WO2025090920A1

WO2025090920A1 - Compositions and methods for treating dysfunction of glucose metabolism and/or regulation

Info

Publication number: WO2025090920A1
Application number: PCT/US2024/053039
Authority: WO
Inventors: Parambir Singh DULAI; Robert Hardie MILLS; Nigel James Boetius MACCLANCY; William J. Hoekstra; Paul Francis MILLER
Original assignee: Piton Therapeutics Inc
Current assignee: Piton Therapeutics Inc
Priority date: 2023-10-25
Filing date: 2024-10-25
Publication date: 2025-05-01
Anticipated expiration: 2026-04-25

Abstract

Aspects of the disclosure relate to compositions and methods for treating one or more symptoms associated with dysfunctions of glucose metabolism and/or regulation. Some embodiments relate to a pharmaceutical dosage form comprising a core comprising an inhibitor of a protease and a controlled release coating applied to an exterior surface of the core. In some cases, the protease inhibitor is a gliptin or a pharmaceutically acceptable salt or other form thereof. In some cases, the protease inhibitor is a compound disclosed herein or a pharmaceutically acceptable salt or other form thereof. In some cases, the controlled release coating is configured to release the protease inhibitor in the large intestine (e.g., colon) and/or small intestine of a subject to whom the pharmaceutical dosage form is administered.

Description

COMPOSITIONS AND METHODS FOR TREATING DYSFUNCTION OF GLUCOSE METABOLISM AND/OR REGULATION RELATED APPLICATIONS This application claims the benefit under 35 U.S.C. § 119(e) of US Provisional Application No. 63/593,191, filed October 25, 2023, entitled “COMPOSITIONS AND METHODS FOR TREATING DYSFUNCTION OF GLUCOSE METABOLISM AND/OR REGULATION” and US Provisional Application No. 63/658,828, filed June 11, 2024, entitled “COMPOSITIONS AND METHODS FOR TREATING DYSFUNCTION OF GLUCOSE METABOLISM AND/OR REGULATION” the content of each of which is hereby incorporated by reference herein in its entirety for all purposes. REFERENCE TO AN ELECTRONIC SEQUENCE LISTING The contents of the electronic sequence listing (P119270004WO00-SEQ-PRW.xml; Size: 2,710 bytes; and Date of Creation: October 22, 2024) are herein incorporated by reference in its entirety. BACKGROUND Deficiencies in the metabolism and regulation of glucose are associated with a variety of symptoms and disorders in a subject, such as insulin resistance, diabetes, endocrine disorders, proliferative diseases, obesity, metabolic syndrome, and malnutrition. Described herein are compositions and methods for modulation of glucose metabolism in a subject. SUMMARY OF INVENTION The present disclosure is related to compositions and methods useful for, in some aspects, modulating glucose metabolism and/or regulation in subject, e.g., for treating diseases and dysfunctions of glucose metabolism and/or regulation. In one aspect, provided is a compound of Formula (I):

or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein: R^b is optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted acyl, optionally substituted heteroaryl, optionally wherein one or more backbone carbon atoms in the optionally substituted alkyl are independently replaced with –O– or –S-; each instance of R¹¹ is independently hydrogen, optionally substituted alkyl, optionally substituted acyl, or a nitrogen protecting group; R^c and R^d are each independently hydrogen, optionally substituted alkyl, halo, -OR^x, or optionally wherein R^c and R^d are joined together to form an optionally substituted C1-6 carbocycle; R^x is hydrogen, optionally substituted alkyl, or an oxygen protecting group; R¹² is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted heterocyclyl, optionally substituted carbocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, or azido; and n is 0, 1, or 2;

provided that the compound is not of the formula: . In another aspect of the present disclosure, provided is a compound of Formula (II):

or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein: each R^a is independently hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted acyl, optionally substituted heteroaryl, or two instances of R^a are joined, including the nitrogen atom to which they are attached, to form an optionally substituted heterocyclyl; R¹ is hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted carbocyclyl, or optionally substituted aryl; R² is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted heteroalkenyl, optionally substituted heteroalkynyl, or optionally substituted acyl; X is hydrogen, hydroxyl, or optionally substituted heteroalkyl; n' is 0, 1, or 2; and provided that the compound is not of the formula:

. Also provided herein, in some aspects, are pharmaceutical compositions comprising compounds disclosed herein or pharmaceutically acceptable salts thereof. In one aspect, a pharmaceutical dosage form is described. In some embodiments, the pharmaceutical dosage form comprises a core comprising an inhibitor of a protease. In certain embodiments, the inhibitor of the protease comprises a compound of Formula (I), a compound of Formula (II), or a pharmaceutically acceptable salt or other form thereof. In certain embodiments, the inhibitor of the protease comprises a gliptin or a pharmaceutically acceptable salt or other form thereof. In certain embodiments, the inhibitor of the protease comprises a compound disclosed herein or a pharmaceutically acceptable salt or other form thereof. In some embodiments, the pharmaceutical dosage form comprises a controlled release coating applied to an exterior surface of the core. In certain embodiments, the controlled release coating is configured to release the inhibitor of the protease in the gastrointestinal tract of a subject to whom the pharmaceutical dosage form is administered. In another aspect, provided is a method of treating a dysfunction of glucose metabolism and/or regulation. In some embodiments, the method comprises delivering a therapeutically effective amount of an inhibitor of a protease to a gastrointestinal tract of a subject. In some embodiments, the method comprises delivering a therapeutically effective amount of a compound of Formula (I), a compound of Formula (II), or a pharmaceutically acceptable salt or other form thereof to the subject. In some embodiments, the method comprises delivering a therapeutically effective amount of a gliptin or a pharmaceutically acceptable salt or other form thereof. In one aspect, provided is a method of treating a dysfunction of glucose metabolism and/or regulation, the method comprising determining an abundance of a bacterial protease in a sample obtained from a subject and delivering a therapeutically effective amount of an inhibitor of the bacterial protease to the gastrointestinal tract of the subject. In certain embodiments, the method comprises determining an abundance of a bacterial protease in a sample obtained from a subject and delivering a therapeutically effective amount of a compound of Formula (I), a compound of Formula (II), or a pharmaceutically acceptable salt or other form thereof to the gastrointestinal tract of the subject. In certain embodiments, the method comprises determining an abundance of a bacterial protease in a sample obtained from a subject and delivering a therapeutically effective amount of a gliptin or a pharmaceutically acceptable salt or other form thereof to the gastrointestinal tract of the subject. The subject matter of the present invention involves, in some cases, interrelated products, alternative solutions to a particular problem, and/or a plurality of different uses of one or more systems and/or articles. Other advantages and novel features of the present invention will become apparent from the following detailed description of various non-limiting embodiments of the invention when considered in conjunction with the accompanying figures. In cases where the present specification and a document incorporated by reference include conflicting and/or inconsistent disclosure, the present specification shall control. BRIEF DESCRIPTION OF THE DRAWINGS Non-limiting embodiments of the present invention will be described by way of example with reference to the accompanying figures, which are schematic and are not intended to be drawn to scale. In the figures, each identical or nearly identical component illustrated is typically represented by a single numeral. For purposes of clarity, not every component is labeled in every figure, nor is every component of each embodiment of the invention shown where illustration is not necessary to allow those of ordinary skill in the art to understand the invention. In the figures: FIG. 1 shows, according to some embodiments, a plot of percent inhibition of B. vulgatus DPP-4 for six gliptins: sitagliptin, linagliptin, teneligliptin, trelagliptin, omarigliptin, and vildagliptin. FIG. 2 shows, according to some embodiments, chemical structures for sitagliptin, vildagliptin, omarigliptin, teneligliptin, linagliptin, alogliptin, and trelagliptin. FIGs. 3A-3B show effects of certain compounds on bodyweight and food intake in diet- induced obesity (DIO) model mice. FIG. 3A shows the effect of treatment by compound 34 and sitagliptin on body weight in the DIO model. Mice were administered vehicle or test compound once a day for 28 days by oral gavage. Body weight of the animals was measured every 2-3 days. Figure shows the percent change in the body weight on Day 27 as compared to the original body weight on Day 1. FIG. 3B shows cumulative feed intake in grams by different groups over the course of 28 days. Two-way ANOVA followed by Kruskal-Wallia test was performed and the different groups are compared to Vehicle (HFD) group; ** p ≤ 0.01, ***p ≤ 0.001. FIGs. 4A-4C shows effects of certain compounds on blood glucose levels in non-fasted and fasted animals. FIG. 4A shows weekly blood glucose levels from non-fasted animals administered compound 34 or sitagliptin, as measured using a glucometer. FIG. 4B-4C show plasma glucose levels in mice that were fasted overnight and administered the compounds by oral gavage 1 hour before a glucose load of 2 gm/kg. Plasma glucose was measured using a glucometer at 0, 10, 30, 60 and 120 min after glucose injection as part of an oral glucose tolerance test (OGTT). FIG. 4B shows plasma glucose levels after an oral glucose tolerance test (OGTT). FIG. 4C shows the area under the curve (AUC) of plasma glucose levels after OGTT. Two-way ANOVA followed by Kruskal-Wallia test was performed and the different groups are compared to Vehicle (HFD) group; ** p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001. FIG. 5 shows plasma level activity of liver function enzymes alanine transaminase (ALT) and aspartate aminotransferase (AST) in groups of mice treated with compound 34, sitagliptin, or vehicle only. Two-way ANOVA followed by Kruskal-Wallia test was performed and the different groups are compared to Vehicle (HFD) group; ** p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001. FIG. 6 shows plasma levels of total cholesterol, high density lipoprotein (HDL), low ^{density lipoprotein (LDL) and triglycerides in mice treated with compound 34, sitagliptin, or} vehicle only. Unpaired t-tests followed by Mann-Whitney test was performed and the different groups are compared to Vehicle (HFD) group; ** p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001. FIGs. 7A-7B show role of bacterial DPP-4 proteases in the human gut. FIG. 7A shows, according to some embodiments, recombinant protease impact on intestinal barrier integrity. FIG. 1 shows a plot of trans-epithelial electrical resistance (“TEER”) (Ω) as a function of time (hours) for T84 intestinal cells without dipeptidyl peptidase-4 (“DPP-4”) (labeled “Cell control”), intestinal cells without DPP-4 and with a protease inhibitor (labeled “Cell control + Protease inhibitor”), intestinal cells with DPP-4 (labeled “DPP-4”), and intestinal cells with DPP-4 and a protease inhibitor (labeled “DPP-4 + Protease inhibitor”). The protease inhibitor was 1x Roche Complete^TM EDTA-Free Protease Inhibitor Cocktail. FIG. 7B shows, according to some embodiments, a chart of percent adherence and invasion of intestinal cells for wild-type B. vulgatus with DPP-4 (left) and B. vulgatus with DPP-4 genetically removed (right). DETAILED DESCRIPTION Aspects of this disclosure relate to compositions and methods useful for modulating (e.g., treating a dysfunction of) glucose metabolism and regulation in a subject. Glucose is a macronutrient essential to several metabolic pathways across species; thus, its availability, storage, and utilization are central to many basic biological functions. In humans, glucose is directly consumed or obtained from food sources which undergo digestion into sugars via a variety of enzymatic pathways in the stomach. Once in the gut (e.g., large intestine and/or small intestine), glucose is absorbed and transferred to the blood stream, where glucose levels are tightly regulated. Glucose in the blood is transported to other tissues and organs for use in a variety of metabolic pathways. Dysfunction of glucose metabolism and regulation is implicated in a variety of diseases and disorders, including, but not limited to, insulin resistance, diabetes, endocrine disorders, obesity, metabolic syndrome, and malnutrition. Traditional drug targets for modulating glucose metabolism in a subject target the activity and availability of host enzymes and hormones; however, the inventors have found that modulation of microbiota activity in the gut may also contribute significantly to the metabolism and regulation of glucose in a subject. In some aspects, the present disclosure relates to administration of compositions comprising a protease inhibitor to a subject (e.g., to the gut of a subject). A protease generally refers to an enzyme that catalyzes proteolysis (e.g., cleavage of one or more peptide bonds to break proteins into smaller polypeptides or single amino acids). The terms “inhibitor of a protease” and “protease inhibitor”, used synonymously herein, generally refer to a compound that reduces or inhibits activity of a protease. In some embodiments, the protease is a bacterial protease. In some embodiments, the protease is a serine protease, a cysteine protease, or a metalloprotease. In certain embodiments, the protease is a serine protease. In certain instances, the serine protease is an S09 type protease (e.g., an S09.13 protease) under the MEROPS classification system. In some embodiments, the protease is configured to cleave GLP-1, GLP-2 and/or GIP. In certain embodiments, the protease is configured to preferentially cleave GLP-2 (e.g., the protease has a higher binding affinity for GLP-2 than for GLP-1 and/or GIP). In some instances, the protease is dipeptidyl peptidase-4 (“DPP-4”). In some embodiments, the protease inhibitor is a compound described herein (e.g., a compound described in the section entitled “Protease Inhibitors" herein) or a pharmaceutically acceptable salt or other form thereof. In some embodiments, the protease inhibitor is a compound of Formula (I) or a pharmaceutically acceptable salt or other form thereof. In some embodiments, the compound of Formula (I) is a compound shown in Table 1 (e.g., a compound of Compound No. 26-57) or a pharmaceutically acceptable salt or other form thereof. In some embodiments, the protease inhibitor is a compound of Formula (II) or a pharmaceutically acceptable salt or other form thereof. In some embodiments, the compound of Formula (II) is a compound shown in Table 2 (e.g., a compound of Compound No. 1-24) or a pharmaceutically acceptable salt or other form thereof. Certain embodiments of Formula (I) and Formula (II) are provided herein (e.g., in the section entitled “Protease Inhibitors”). In some embodiments, the protease inhibitor is a gliptin or a pharmaceutically acceptable salt or other form thereof. The term “gliptin” generally refers to a functional class of compounds that inhibit human dipeptidyl peptidase-4 (“DPP-4”). DPP-4 is an serine peptidase/prolyl oligopeptidase which cleaves certain peptides/proteins containing a proline or an alanine at position 2 of their N-terminus (see, e.g., Mulvihill and Drucker, Endocr Rev. 2014 Dec 1; 35(6): 992–1019). Human DPP-4 is expressed in subcutaneous and visceral adipose deposits in the gut, liver lung, and kidney, allowing access to circulating peptides for inactivation, such as glucagon- like peptide-1 (“GLP-1”), glucagon-like peptide-2 (“GLP-2”), and glucose-dependent insulinotropic peptide (also known as “gastric inhibitory peptide”; “GIP”). GLP-1,GLP-2, and GIP are hormones that are secreted by enteroendocrine L-cells and K-cells in the gastrointestinal ^{(“GI”) tract (e.g., in the ileum, large intestine). GLP-1, GLP-2, and GIP are secreted after} increases in glucose levels in the blood (e.g., after meal ingestion) and, among other functions, stimulate release of insulin. GLP-2 has numerous cytoprotective, reparative, and energy- retentive functions, including but not limited to, increasing the barrier function of the gut epithelium, regulating gastric motility and gastric acid secretion, stimulating crypt cell proliferation, and inhibiting apoptosis in the enterocyte and crypt compartments. GLP-1 and GIP also perform a variety of functions, including but not limited to stimulation of secretion of insulin and reduction of glucagon release, thereby decreasing glucose levels in the blood. By blocking the activity of human DPP-4, gliptins can disinhibit these glucoregulatory hormones, indirectly acting to reduce glucose levels in the blood, which may be useful for diseases and disorders related to glucose regulation; indeed, a number of known gliptins targeting human DPP-4 (e.g., sitagliptin, saxagliptin, linagliptin, and alogliptin) have been approved by the U.S. Food and Drug Administration (“FDA”) for oral administration for treatment of type 2 diabetes mellitus. Though gliptins are typically associated with modulation of human proteases for regulation of glucose metabolism, the inventors of the present disclosure have discovered that inhibition of bacterial proteases (e.g., DPP-4) may promote treatment and/or prevention of one or more symptoms associated with dysfunction of glucose metabolism and/or regulation, for example, by reducing excessive cleavage of GLP-1, GLP-2, and/or GIP. The inventors have also developed several novel compounds which may be suitable for preventing, alleviating, or arresting one or more symptoms of dysfunctional glucose metabolism and/or regulation in a subject, or otherwise providing desired side effects (e.g., weight loss). As described in further detail herein, the inventors have recognized and appreciated that administration of one or more protease inhibitors (e.g., a gliptin and/or a compound described herein) to a subject diagnosed with, or at risk of developing, a dysfunction of glucose metabolism and/or regulation may advantageously prevent, alleviate, or arrest one or more symptoms of the same in the subject. The inventors have further recognized and appreciated that, in cases of oral administration of a protease inhibitor (e.g., gliptins and/or compounds described herein), it may be desirable to facilitate targeted delivery of the protease inhibitor to a particular location within the gastrointestinal (“GI”) tract (e.g., the gut) of a subject, for example, to enhance treatment efficacy, reduce systemic drug exposure and associated toxicity, and/or improve drug bioavailability. Accordingly, some embodiments relate to methods comprising delivering an effective amount (e.g., therapeutically effective amount) of a protease inhibitor (e.g., a gliptin ^{and/or compound described herein) to the large intestine (e.g., colon) and/or small intestine of a} subject. Definitions Definitions of specific functional groups and chemical terms are described in more detail below. The chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75^th Ed., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in Thomas Sorrell, Organic Chemistry, University Science Books, Sausalito, 1999;Michael B. Smith, March’s Advanced Organic Chemistry, 7^th Edition, John Wiley & Sons, Inc., New York, 2013; Richard C. Larock, Comprehensive Organic Transformations, John Wiley & Sons, Inc., New York, 2018; and Carruthers, Some Modern Methods of Organic Synthesis, 3^rd Edition, Cambridge University Press, Cambridge, 1987. Compounds described herein can comprise one or more asymmetric centers, and thus can exist in various stereoisomeric forms, e.g., enantiomers and/or diastereomers. For example, the compounds described herein can be in the form of an individual enantiomer, diastereomer or geometric isomer, or can be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomer. Isomers can be isolated from mixtures by methods known to those skilled in the art, including chiral high pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers can be prepared by asymmetric syntheses. See, for example, Jacques et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen et al., Tetrahedron 33:2725 (1977); Eliel, E.L. Stereochemistry of Carbon Compounds (McGraw–Hill, NY, 1962); and Wilen, S.H., Tables of Resolving Agents and Optical Resolutions p. 268 (E.L. Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972). The present disclosure additionally encompasses compounds as individual isomers substantially free of other isomers, and alternatively, as mixtures of various isomers. Unless otherwise provided, formulae and structures depicted herein include compounds that do not include isotopically enriched atoms, and also include compounds that include isotopically enriched atoms. For example, compounds having the present structures except for the replacement of hydrogen by deuterium or tritium, replacement of ¹⁹F with ¹⁸F, or the replacement of a carbon by a ¹³C- or ¹⁴C-enriched carbon are within the scope of the disclosure. Such compounds are useful, for example, as analytical tools or probes in biological assays. The term “isotopes” refers to variants of a particular chemical element such that, while all isotopes of a given element share the same number of protons in each atom of the element, those isotopes differ in the number of neutrons. The term “radioactivity” or “radioactive decay” refers to the process by which a nucleus of an unstable isotope (e.g., ¹⁸F) loses energy by emitting particles or rays (e.g., alpha particles, beta particles, and gamma rays) of ionizing radiation. Such an unstable isotope or a material including the unstable isotope is referred to as “radioactive.” The Curie (Ci) is a non-SI (non-International System of Units) unit of radioactivity and is defined as 1 Ci = 3.7 × 10¹⁰ decays per second. The term “specific activity” refers to the unit radioactivity of a material (e.g., a compound of disclosed herein, or a salt, tautomer, stereoisomer, or isotopically labeled derivative (e.g., ¹⁸F labeled derivative) thereof). In certain embodiments, the term “specific activity” refers to the radioactivity of a material per micromole (mmol) of the material. When a range of values (“range”) is listed, it encompasses each value and sub-range within the range. A range is inclusive of the values at the two ends of the range unless otherwise provided. For example, “C1-6 alkyl” encompasses, C1, C2, C3, C4, C5, C6, C1–6, C1–5, C1–4, C1–3, C_1–2, C_2–6, C_2–5, C_2–4, C_2–3, C_3–6, C_3–5, C_3–4, C_4–6, C_4–5, and C_5–6 alkyl. The term “aliphatic” refers to alkyl, alkenyl, alkynyl, and carbocyclic groups. Likewise, the term “heteroaliphatic” refers to heteroalkyl, heteroalkenyl, heteroalkynyl, and heterocyclic groups. The term “alkyl” refers to a radical of a straight-chain or branched saturated hydrocarbon group having from 1 to 20 carbon atoms (“C1–20 alkyl”). In some embodiments, an alkyl group has 1 to 12 carbon atoms (“C_1–12 alkyl”). In some embodiments, an alkyl group has 1 to 10 carbon atoms (“C_1–10 alkyl”). In some embodiments, an alkyl group has 1 to 9 carbon atoms (“C1–9 alkyl”). In some embodiments, an alkyl group has 1 to 8 carbon atoms (“C1–8 alkyl”). In some embodiments, an alkyl group has 1 to 7 carbon atoms (“C_1–7 alkyl”). In some embodiments, an alkyl group has 1 to 6 carbon atoms (“C_1–6 alkyl”). In some embodiments, an alkyl group has 1 to 5 carbon atoms (“C1–5 alkyl”). In some embodiments, an alkyl group has 1 to 4 carbon atoms (“C_1–4 alkyl”). In some embodiments, an alkyl group has 1 to 3 carbon atoms (“C_1–3 alkyl”). In some embodiments, an alkyl group has 1 to 2 carbon atoms (“C_1–2 alkyl”). In some embodiments, an alkyl group has 1 carbon atom (“C1 alkyl”). In some embodiments, an alkyl group has 2 to 6 carbon atoms (“C2-6 alkyl”). Examples of C1–6 alkyl groups include methyl (C₁), ethyl (C₂), propyl (C₃) (e.g., n-propyl, isopropyl), butyl (C₄) (e.g., n-butyl, tert-butyl, sec- butyl, isobutyl), pentyl (C5) (e.g., n-pentyl, 3-pentanyl, amyl, neopentyl, 3-methyl-2-butanyl, tert-amyl), and hexyl (C6) (e.g., n-hexyl). Additional examples of alkyl groups include n-heptyl (C₇), n-octyl (C₈), n-dodecyl (C₁₂), and the like. Unless otherwise specified, each instance of an alkyl group is independently unsubstituted (an “unsubstituted alkyl”) or substituted (a “substituted alkyl”) with one or more substituents (e.g., halogen, such as F). In certain embodiments, the alkyl group is an unsubstituted C_1–12 alkyl (such as unsubstituted C_1–6 alkyl, e.g., −CH3 (Me), unsubstituted ethyl (Et), unsubstituted propyl (Pr, e.g., unsubstituted n-propyl (n-Pr), unsubstituted isopropyl (i-Pr)), unsubstituted butyl (Bu, e.g., unsubstituted n-butyl (n- Bu), unsubstituted tert-butyl (tert-Bu or t-Bu), unsubstituted sec-butyl (sec-Bu or s-Bu), unsubstituted isobutyl (i-Bu)). In certain embodiments, the alkyl group is a substituted C_1–12 alkyl (such as substituted C1–6 alkyl, e.g., –CH2F, –CHF2, –CF3, –CH2CH2F, –CH2CHF2, – CH2CF3, or benzyl (Bn)). The term “haloalkyl” is a substituted alkyl group, wherein one or more of the hydrogen atoms are independently replaced by a halogen, e.g., fluoro, bromo, chloro, or iodo. “Perhaloalkyl” is a subset of haloalkyl, and refers to an alkyl group wherein all of the hydrogen atoms are independently replaced by a halogen, e.g., fluoro, bromo, chloro, or iodo. In some embodiments, the haloalkyl moiety has 1 to 20 carbon atoms (“C1–20 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 10 carbon atoms (“C1–10 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 9 carbon atoms (“C_1–9 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 8 carbon atoms (“C1–8 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 7 carbon atoms (“C1–7 haloalkyl”).In some embodiments, the haloalkyl moiety has 1 to 6 carbon atoms (“C_1–6 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 5 carbon atoms (“C1–5 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 4 carbon atoms (“C1–4 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 3 carbon atoms (“C_1–3 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 2 carbon atoms (“C1–2 haloalkyl”). In some embodiments, all of the haloalkyl hydrogen atoms are independently replaced with fluoro to provide a “perfluoroalkyl” group. In some embodiments, all of the haloalkyl hydrogen atoms are independently replaced with chloro to provide a “perchloroalkyl” group. Examples of haloalkyl groups include –CHF2, −CH2F, −CF3, −CH2CF3, −CF2CF3, −CF2CF2CF3, −CCl3, −CFCl2, −CF₂Cl, and the like. The term “heteroalkyl” refers to an alkyl group, which further includes at least one heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen, nitrogen, or sulfur within (e.g., inserted between adjacent carbon atoms of) and/or placed at one or more terminal position(s) of the parent chain. In certain embodiments, a heteroalkyl group refers to a saturated group having from 1 to 20 carbon atoms and 1 or more heteroatoms within the parent chain (“heteroC_1–20 alkyl”). In certain embodiments, a heteroalkyl group refers to a saturated group having from 1 to 12 carbon atoms and 1 or more heteroatoms within the parent chain (“heteroC1–12 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 11 carbon atoms and 1 or more heteroatoms within the parent chain (“heteroC1–11 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 10 carbon atoms and 1 or more heteroatoms within the parent chain (“heteroC_1–10 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 9 carbon atoms and 1 or more heteroatoms within the parent chain (“heteroC1–9 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 8 carbon atoms and 1 or more heteroatoms within the parent chain (“heteroC1–8 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 7 carbon atoms and 1 or more heteroatoms within the parent chain (“heteroC1–7 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 6 carbon atoms and 1 or more heteroatoms within the parent chain (“heteroC_1–6 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 5 carbon atoms and 1 or 2 heteroatoms within the parent chain (“heteroC1–5 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 4 carbon atoms and 1or 2 heteroatoms within the parent chain (“heteroC_1–4 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 3 carbon atoms and 1 heteroatom within the parent chain (“heteroC1–3 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 2 carbon atoms and 1 heteroatom within the parent chain (“heteroC_1–2 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 carbon atom and 1 heteroatom (“heteroC1 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 2 to 6 carbon atoms and 1 or 2 heteroatoms within the parent chain (“heteroC_2-6 alkyl”). Unless otherwise specified, each instance of a heteroalkyl group is independently unsubstituted (an “unsubstituted heteroalkyl”) or substituted (a “substituted heteroalkyl”) with one or more substituents. In certain embodiments, the heteroalkyl group is an unsubstituted heteroC_1–12 alkyl. In certain embodiments, the heteroalkyl group is a substituted heteroC_1–12 alkyl. The term “alkenyl” refers to a radical of a straight-chain or branched hydrocarbon group ^{having from 1 to 20 carbon atoms and one or more carbon-carbon double bonds (e.g., 1, 2, 3, or} 4 double bonds). In some embodiments, an alkenyl group has 1 to 20 carbon atoms (“C_1-20 alkenyl”). In some embodiments, an alkenyl group has 1 to 12 carbon atoms (“C1–12 alkenyl”). In some embodiments, an alkenyl group has 1 to 11 carbon atoms (“C_1–11 alkenyl”). In some embodiments, an alkenyl group has 1 to 10 carbon atoms (“C1–10 alkenyl”). In some embodiments, an alkenyl group has 1 to 9 carbon atoms (“C_1–9 alkenyl”). In some embodiments, an alkenyl group has 1 to 8 carbon atoms (“C1–8 alkenyl”). In some embodiments, an alkenyl group has 1 to 7 carbon atoms (“C1–7 alkenyl”). In some embodiments, an alkenyl group has 1 to 6 carbon atoms (“C_1–6 alkenyl”). In some embodiments, an alkenyl group has 1 to 5 carbon atoms (“C1–5 alkenyl”). In some embodiments, an alkenyl group has 1 to 4 carbon atoms (“C1–4 alkenyl”). In some embodiments, an alkenyl group has 1 to 3 carbon atoms (“C1–3 alkenyl”). In some embodiments, an alkenyl group has 1 to 2 carbon atoms (“C_1–2 alkenyl”). In some embodiments, an alkenyl group has 1 carbon atom (“C₁ alkenyl”). The one or more carbon- carbon double bonds can be internal (such as in 2-butenyl) or terminal (such as in 1-butenyl). Examples of C1–4 alkenyl groups include methylidenyl (C1), ethenyl (C2), 1-propenyl (C3), 2- propenyl (C₃), 1-butenyl (C₄), 2-butenyl (C₄), butadienyl (C₄), and the like. Examples of C_1–6 alkenyl groups include the aforementioned C2-4 alkenyl groups as well as pentenyl (C5), pentadienyl (C5), hexenyl (C6), and the like. Additional examples of alkenyl include heptenyl (C₇), octenyl (C₈), octatrienyl (C₈), and the like. Unless otherwise specified, each instance of an alkenyl group is independently unsubstituted (an “unsubstituted alkenyl”) or substituted (a “substituted alkenyl”) with one or more substituents. In certain embodiments, the alkenyl group is an unsubstituted C_1-20 alkenyl. In certain embodiments, the alkenyl group is a substituted C_1-20 alkenyl. In an alkenyl group, a C=C double bond for which the stereochemistry is not specified

-configuration. The term “heteroalkenyl” refers to an alkenyl group, which further includes at least one heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen, nitrogen, or sulfur within (e.g., inserted between adjacent carbon atoms of) and/or placed at one or more terminal position(s) of the parent chain. In certain embodiments, a heteroalkenyl group refers to a group having from 1 to 20 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain (“heteroC_1–20 alkenyl”). In certain embodiments, a heteroalkenyl group refers to a group having from 1 to 12 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain (“heteroC1–12 alkenyl”). In certain embodiments, a heteroalkenyl group refers to a group having from 1 to 11 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain (“heteroC_1–11 alkenyl”). In certain embodiments, a heteroalkenyl group refers to a group having from 1 to 10 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain (“heteroC1–10 alkenyl”). In some embodiments, a heteroalkenyl group has 1 to 9 carbon atoms at least one double bond, and 1 or more heteroatoms within the parent chain (“heteroC_1–9 alkenyl”). In some embodiments, a heteroalkenyl group has 1 to 8 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain (“heteroC1–8 alkenyl”). In some embodiments, a heteroalkenyl group has 1 to 7 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain (“heteroC1–7 alkenyl”). In some embodiments, a heteroalkenyl group has 1to 6 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain (“heteroC_1–6 alkenyl”). In some embodiments, a heteroalkenyl group has 1 to 5 carbon atoms, at least one double bond, and 1 or 2 heteroatoms within the parent chain (“heteroC1–5 alkenyl”). In some embodiments, a heteroalkenyl group has 1 to 4 carbon atoms, at least one double bond, and 1 or 2 heteroatoms within the parent chain (“heteroC_1–4 alkenyl”). In some embodiments, a heteroalkenyl group has 1 to 3 carbon atoms, at least one double bond, and 1 heteroatom within the parent chain (“heteroC1–3 alkenyl”). In some embodiments, a heteroalkenyl group has 1 to 2 carbon atoms, at least one double bond, and 1 heteroatom within the parent chain (“heteroC_1–2 alkenyl”). In some embodiments, a heteroalkenyl group has 1 to 6 carbon atoms, at least one double bond, and 1 or 2 heteroatoms within the parent chain (“heteroC1–6 alkenyl”). Unless otherwise specified, each instance of a heteroalkenyl group is independently unsubstituted (an “unsubstituted heteroalkenyl”) or substituted (a “substituted heteroalkenyl”) with one or more substituents. In certain embodiments, the heteroalkenyl group is an unsubstituted heteroC1–20 alkenyl. In certain embodiments, the heteroalkenyl group is a substituted heteroC_1–20 alkenyl. The term “alkynyl” refers to a radical of a straight-chain or branched hydrocarbon group having from 1 to 20 carbon atoms and one or more carbon-carbon triple bonds (e.g., 1, 2, 3, or 4 triple bonds) (“C_1-20 alkynyl”). In some embodiments, an alkynyl group has 1 to 10 carbon atoms (“C1-10 alkynyl”). In some embodiments, an alkynyl group has 1 to 9 carbon atoms (“C1-9 alkynyl”). In some embodiments, an alkynyl group has 1 to 8 carbon atoms (“C1-8 alkynyl”). In some embodiments, an alkynyl group has 1 to 7 carbon atoms (“C_1-7 alkynyl”). In some embodiments, an alkynyl group has 1 to 6 carbon atoms (“C_1-6 alkynyl”). In some embodiments, an alkynyl group has 1 to 5 carbon atoms (“C1-5 alkynyl”). In some embodiments, an alkynyl ^{group has 1 to 4 carbon atoms (“C} _1-4 ^{alkynyl”). In some embodiments, an alkynyl group has 1 to} 3 carbon atoms (“C_1-3 alkynyl”). In some embodiments, an alkynyl group has 1 to 2 carbon atoms (“C1-2 alkynyl”). In some embodiments, an alkynyl group has 1 carbon atom (“C1 alkynyl”). The one or more carbon-carbon triple bonds can be internal (such as in 2-butynyl) or terminal (such as in 1-butynyl). Examples of C1-4 alkynyl groups include, without limitation, methylidynyl (C₁), ethynyl (C₂), 1-propynyl (C₃), 2-propynyl (C₃), 1-butynyl (C₄), 2-butynyl (C4), and the like. Examples of C1-6 alkenyl groups include the aforementioned C2-4 alkynyl groups as well as pentynyl (C5), hexynyl (C6), and the like. Additional examples of alkynyl include heptynyl (C₇), octynyl (C₈), and the like. Unless otherwise specified, each instance of an alkynyl group is independently unsubstituted (an “unsubstituted alkynyl”) or substituted (a “substituted alkynyl”) with one or more substituents. In certain embodiments, the alkynyl group is an unsubstituted C_1-20 alkynyl. In certain embodiments, the alkynyl group is a substituted C_1-20 alkynyl. The term “heteroalkynyl” refers to an alkynyl group, which further includes at least one heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen, nitrogen, or sulfur within (e.g., inserted between adjacent carbon atoms of) and/or placed at one or more terminal position(s) of the parent chain. In certain embodiments, a heteroalkynyl group refers to a group having from 1 to 20 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain (“heteroC_1–20 alkynyl”). In certain embodiments, a heteroalkynyl group refers to a group having from 1 to 10 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain (“heteroC1–10 alkynyl”). In some embodiments, a heteroalkynyl group has 1 to 9 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain (“heteroC_1–9 alkynyl”). In some embodiments, a heteroalkynyl group has 1 to 8 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain (“heteroC1–8 alkynyl”). In some embodiments, a heteroalkynyl group has 1 to 7 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain (“heteroC1–7 alkynyl”). In some embodiments, a heteroalkynyl group has 1 to 6 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain (“heteroC_1–6 alkynyl”). In some embodiments, a heteroalkynyl group has 1 to 5 carbon atoms, at least one triple bond, and 1 or 2 heteroatoms within the parent chain (“heteroC1–5 alkynyl”). In some embodiments, a heteroalkynyl group has 1 to 4 carbon atoms, at least one triple bond, and 1or 2 heteroatoms within the parent chain (“heteroC_1–4 alkynyl”). In some embodiments, a heteroalkynyl group has 1 to 3 carbon atoms, at least one triple bond, and 1 heteroatom within the parent chain (“heteroC1–3 alkynyl”). In some embodiments, a ^{heteroalkynyl group has 1 to 2 carbon atoms, at least one triple bond, and 1 heteroatom within} the parent chain (“heteroC_1–2 alkynyl”). In some embodiments, a heteroalkynyl group has 1 to 6 carbon atoms, at least one triple bond, and 1 or 2 heteroatoms within the parent chain (“heteroC_1–6 alkynyl”). Unless otherwise specified, each instance of a heteroalkynyl group is independently unsubstituted (an “unsubstituted heteroalkynyl”) or substituted (a “substituted heteroalkynyl”) with one or more substituents. In certain embodiments, the heteroalkynyl group is an unsubstituted heteroC1–20 alkynyl. In certain embodiments, the heteroalkynyl group is a substituted heteroC1–20 alkynyl. The term “carbocyclyl” or “carbocyclic” refers to a radical of a non-aromatic cyclic hydrocarbon group having from 3 to 14 ring carbon atoms (“C3-14 carbocyclyl”) and zero heteroatoms in the non-aromatic ring system. In some embodiments, a carbocyclyl group has 3 to 14 ring carbon atoms (“C_3-14 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 13 ring carbon atoms (“C_3-13 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 12 ring carbon atoms (“C3-12 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 11 ring carbon atoms (“C3-11 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 10 ring carbon atoms (“C_3-10 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 8 ring carbon atoms (“C3-8 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 7 ring carbon atoms (“C3-7 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 6 ring carbon atoms (“C_3-6 carbocyclyl”). In some embodiments, a carbocyclyl group has 4 to 6 ring carbon atoms (“C4-6 carbocyclyl”). In some embodiments, a carbocyclyl group has 5 to 6 ring carbon atoms (“C5-6 carbocyclyl”). In some embodiments, a carbocyclyl group has 5 to 10 ring carbon atoms (“C_5-10 carbocyclyl”). Exemplary C_3-6 carbocyclyl groups include cyclopropyl (C3), cyclopropenyl (C3), cyclobutyl (C4), cyclobutenyl (C4), cyclopentyl (C5), cyclopentenyl (C5), cyclohexyl (C6), cyclohexenyl (C6), cyclohexadienyl (C6), and the like. Exemplary C3-8 carbocyclyl groups include the aforementioned C_3-6 carbocyclyl groups as well as cycloheptyl (C7), cycloheptenyl (C7), cycloheptadienyl (C7), cycloheptatrienyl (C7), cyclooctyl (C8), cyclooctenyl (C8), bicyclo[2.2.1]heptanyl (C7), bicyclo[2.2.2]octanyl (C8), and the like. Exemplary C_3-10 carbocyclyl groups include the aforementioned C_3-8 carbocyclyl groups as well as cyclononyl (C9), cyclononenyl (C9), cyclodecyl (C10), cyclodecenyl (C10), octahydro-1H- indenyl (C9), decahydronaphthalenyl (C10), spiro[4.5]decanyl (C10), and the like. Exemplary C3-8 carbocyclyl groups include the aforementioned C_3-10 carbocyclyl groups as well as cycloundecyl (C₁₁), spiro[5.5]undecanyl (C₁₁), cyclododecyl (C₁₂), cyclododecenyl (C₁₂), cyclotridecane (C₁₃), cyclotetradecane (C14), and the like. As the foregoing examples illustrate, in certain ^{embodiments, the carbocyclyl group is either monocyclic (“monocyclic carbocyclyl”) or} polycyclic (e.g., containing a fused, bridged or spiro ring system such as a bicyclic system (“bicyclic carbocyclyl”) or tricyclic system (“tricyclic carbocyclyl”)) and can be saturated or can contain one or more carbon-carbon double or triple bonds. “Carbocyclyl” also includes ring systems wherein the carbocyclyl ring, as defined above, is fused with one or more aryl or heteroaryl groups wherein the point of attachment is on the carbocyclyl ring, and in such instances, the number of carbons continue to designate the number of carbons in the carbocyclic ring system. Unless otherwise specified, each instance of a carbocyclyl group is independently unsubstituted (an “unsubstituted carbocyclyl”) or substituted (a “substituted carbocyclyl”) with one or more substituents. In certain embodiments, the carbocyclyl group is an unsubstituted C3-14 carbocyclyl. In certain embodiments, the carbocyclyl group is a substituted C3-14 carbocyclyl. In some embodiments, “carbocyclyl” is a monocyclic, saturated carbocyclyl group having from 3 to 14 ring carbon atoms (“C_3-14 cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 10 ring carbon atoms (“C3-10 cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 8 ring carbon atoms (“C3-8 cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 6 ring carbon atoms (“C_3-6 cycloalkyl”). In some embodiments, a cycloalkyl group has 4 to 6 ring carbon atoms (“C4-6 cycloalkyl”). In some embodiments, a cycloalkyl group has 5 to 6 ring carbon atoms (“C5-6 cycloalkyl”). In some embodiments, a cycloalkyl group has 5 to 10 ring carbon atoms (“C_5-10 cycloalkyl”). Examples of C_5-6 cycloalkyl groups include cyclopentyl (C5) and cyclohexyl (C5). Examples of C3-6 cycloalkyl groups include the aforementioned C5-6 cycloalkyl groups as well as cyclopropyl (C3) and cyclobutyl (C4). Examples of C_3-8 cycloalkyl groups include the aforementioned C_3-6 cycloalkyl groups as well as cycloheptyl (C7) and cyclooctyl (C8). Unless otherwise specified, each instance of a cycloalkyl group is independently unsubstituted (an “unsubstituted cycloalkyl”) or substituted (a “substituted cycloalkyl”) with one or more substituents. In certain embodiments, the cycloalkyl group is an unsubstituted C3-14 cycloalkyl. In certain embodiments, the cycloalkyl group is a substituted C3-14 cycloalkyl. In certain embodiments, the carbocyclyl includes 0, 1, or 2 C=C double bonds in the carbocyclic ring system, as valency permits. The term “heterocyclyl” or “heterocyclic” refers to a radical of a 3- to 14-membered non- aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“3–14 membered heterocyclyl”). In heterocyclyl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. A heterocyclyl group can ^{either be monocyclic (“monocyclic heterocyclyl”) or polycyclic (e.g., a fused, bridged or spiro} ring system such as a bicyclic system (“bicyclic heterocyclyl”) or tricyclic system (“tricyclic heterocyclyl”)), and can be saturated or can contain one or more carbon-carbon double or triple bonds. Heterocyclyl polycyclic ring systems can include one or more heteroatoms in one or both rings. “Heterocyclyl” also includes ring systems wherein the heterocyclyl ring, as defined above, is fused with one or more carbocyclyl groups wherein the point of attachment is either on the carbocyclyl or heterocyclyl ring, or ring systems wherein the heterocyclyl ring, as defined above, is fused with one or more aryl or heteroaryl groups, wherein the point of attachment is on the heterocyclyl ring, and in such instances, the number of ring members continue to designate the number of ring members in the heterocyclyl ring system. Unless otherwise specified, each instance of heterocyclyl is independently unsubstituted (an “unsubstituted heterocyclyl”) or substituted (a “substituted heterocyclyl”) with one or more substituents. In certain embodiments, the heterocyclyl group is an unsubstituted 3–14 membered heterocyclyl. In certain embodiments, the heterocyclyl group is a substituted 3–14 membered heterocyclyl. In certain embodiments, the heterocyclyl is substituted or unsubstituted, 3- to 7-membered, monocyclic heterocyclyl, wherein 1, 2, or 3 atoms in the heterocyclic ring system are independently oxygen, nitrogen, or sulfur, as valency permits. In some embodiments, a heterocyclyl group is a 5–10 membered non-aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–10 membered heterocyclyl”). In some embodiments, a heterocyclyl group is a 5–8 membered non-aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–8 membered heterocyclyl”). In some embodiments, a heterocyclyl group is a 5–6 membered non-aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–6 membered heterocyclyl”). In some embodiments, the 5–6 membered heterocyclyl has 1–3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5–6 membered heterocyclyl has 1–2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5–6 membered heterocyclyl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur. Exemplary 3-membered heterocyclyl groups containing 1 heteroatom include aziridinyl, oxiranyl, and thiiranyl. Exemplary 4-membered heterocyclyl groups containing 1 heteroatom include azetidinyl, oxetanyl, and thietanyl. Exemplary 5-membered heterocyclyl groups ^{containing 1 heteroatom include tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl,} dihydrothiophenyl, pyrrolidinyl, dihydropyrrolyl, and pyrrolyl-2,5-dione. Exemplary 5- membered heterocyclyl groups containing 2 heteroatoms include dioxolanyl, oxathiolanyl and dithiolanyl. Exemplary 5-membered heterocyclyl groups containing 3 heteroatoms include triazolinyl, oxadiazolinyl, and thiadiazolinyl. Exemplary 6-membered heterocyclyl groups containing 1 heteroatom include piperidinyl, tetrahydropyranyl, dihydropyridinyl, and thianyl. Exemplary 6-membered heterocyclyl groups containing 2 heteroatoms include piperazinyl, morpholinyl, dithianyl, and dioxanyl. Exemplary 6-membered heterocyclyl groups containing 3 heteroatoms include triazinyl. Exemplary 7-membered heterocyclyl groups containing 1 heteroatom include azepanyl, oxepanyl and thiepanyl. Exemplary 8-membered heterocyclyl groups containing 1 heteroatom include azocanyl, oxecanyl and thiocanyl. Exemplary bicyclic heterocyclyl groups include indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, tetrahydrobenzothienyl, tetrahydrobenzofuranyl, tetrahydroindolyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, decahydroisoquinolinyl, octahydrochromenyl, octahydroisochromenyl, decahydronaphthyridinyl, decahydro-1,8-naphthyridinyl, octahydropyrrolo[3,2-b]pyrrole, indolinyl, phthalimidyl, naphthalimidyl, chromanyl, chromenyl, 1H-benzo[e][1,4]diazepinyl, 1,4,5,7-tetrahydropyrano[3,4-b]pyrrolyl, 5,6-dihydro-4H-furo[3,2- b]pyrrolyl, 6,7-dihydro-5H-furo[3,2-b]pyranyl, 5,7-dihydro-4H-thieno[2,3-c]pyranyl, 2,3- dihydro-1H-pyrrolo[2,3-b]pyridinyl, 2,3-dihydrofuro[2,3-b]pyridinyl, 4,5,6,7-tetrahydro-1H- pyrrolo[2,3-b]pyridinyl, 4,5,6,7-tetrahydrofuro[3,2-c]pyridinyl, 4,5,6,7-tetrahydrothieno[3,2- b]pyridinyl, 1,2,3,4-tetrahydro-1,6-naphthyridinyl, and the like. The term “aryl” refers to a radical of a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 p electrons shared in a cyclic array) having 6–14 ring carbon atoms and zero heteroatoms provided in the aromatic ring system (“C6-14 aryl”). In some embodiments, an aryl group has 6 ring carbon atoms (“C6 aryl”; e.g., phenyl). In some embodiments, an aryl group has 10 ring carbon atoms (“C₁₀ aryl”; e.g., naphthyl such as 1–naphthyl and 2-naphthyl). In some embodiments, an aryl group has 14 ring carbon atoms (“C14 aryl”; e.g., anthracyl). “Aryl” also includes ring systems wherein the aryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the radical or point of attachment is on the aryl ring, and in such instances, the number of carbon atoms continue to designate the number of carbon atoms in the aryl ring system. Unless otherwise specified, each instance of an aryl group is independently unsubstituted (an “unsubstituted aryl”) or substituted (a “substituted aryl”) with one or more substituents. In certain embodiments, the aryl group is an unsubstituted C6-14 aryl. In certain embodiments, the aryl group is a substituted C6-14 aryl. “Aralkyl” is a subset of “alkyl” and refers to an alkyl group substituted by an aryl group, wherein the point of attachment is on the alkyl moiety. The term “heteroaryl” refers to a radical of a 5-14 membered monocyclic or polycyclic (e.g., bicyclic, tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 p electrons shared in a cyclic array) having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-14 membered heteroaryl”). In heteroaryl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. Heteroaryl polycyclic ring systems can include one or more heteroatoms in one or both rings. “Heteroaryl” includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the point of attachment is on the heteroaryl ring, and in such instances, the number of ring members continue to designate the number of ring members in the heteroaryl ring system. “Heteroaryl” also includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more aryl groups wherein the point of attachment is either on the aryl or heteroaryl ring, and in such instances, the number of ring members designates the number of ring members in the fused polycyclic (aryl/heteroaryl) ring system. Polycyclic heteroaryl groups wherein one ring does not contain a heteroatom (e.g., indolyl, quinolinyl, carbazolyl, and the like) the point of attachment can be on either ring, e.g., either the ring bearing a heteroatom (e.g., 2-indolyl) or the ring that does not contain a heteroatom (e.g., 5-indolyl). In certain embodiments, the heteroaryl is substituted or unsubstituted, 5- or 6-membered, monocyclic heteroaryl, wherein 1, 2, 3, or 4 atoms in the heteroaryl ring system are independently oxygen, nitrogen, or sulfur. In certain embodiments, the heteroaryl is substituted or unsubstituted, 9- or 10-membered, bicyclic heteroaryl, wherein 1, 2, 3, or 4 atoms in the heteroaryl ring system are independently oxygen, nitrogen, or sulfur. In some embodiments, a heteroaryl group is a 5-10 membered aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-10 membered heteroaryl”). In some embodiments, a heteroaryl group is a 5-8 membered aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-8 membered heteroaryl”). In some embodiments, a heteroaryl group is a 5-6 membered aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-6 membered heteroaryl”). In some embodiments, the 5-6 membered heteroaryl has 1–3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6 membered heteroaryl has 1–2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6 membered heteroaryl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur. Unless otherwise specified, each instance of a heteroaryl group is independently unsubstituted (an “unsubstituted heteroaryl”) or substituted (a “substituted heteroaryl”) with one or more substituents. In certain embodiments, the heteroaryl group is an unsubstituted 5-14 membered heteroaryl. In certain embodiments, the heteroaryl group is a substituted 5-14 membered heteroaryl. Exemplary 5-membered heteroaryl groups containing 1 heteroatom include pyrrolyl, furanyl, and thiophenyl. Exemplary 5-membered heteroaryl groups containing 2 heteroatoms include imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl. Exemplary 5- membered heteroaryl groups containing 3 heteroatoms include triazolyl, oxadiazolyl, and thiadiazolyl. Exemplary 5-membered heteroaryl groups containing 4 heteroatoms include tetrazolyl. Exemplary 6-membered heteroaryl groups containing 1 heteroatom include pyridinyl. Exemplary 6-membered heteroaryl groups containing 2 heteroatoms include pyridazinyl, pyrimidinyl, and pyrazinyl. Exemplary 6-membered heteroaryl groups containing 3 or 4 heteroatoms include triazinyl and tetrazinyl, respectively. Exemplary 7-membered heteroaryl groups containing 1 heteroatom include azepinyl, oxepinyl, and thiepinyl. Exemplary 5,6- bicyclic heteroaryl groups include indolyl, isoindolyl, indazolyl, benzotriazolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, benzoisofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzoxadiazolyl, benzthiazolyl, benzisothiazolyl, benzthiadiazolyl, indolizinyl, and purinyl. Exemplary 6,6-bicyclic heteroaryl groups include naphthyridinyl, pteridinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl. Exemplary tricyclic heteroaryl groups include phenanthridinyl, dibenzofuranyl, carbazolyl, acridinyl, phenothiazinyl, phenoxazinyl, and phenazinyl. “Heteroaralkyl” is a subset of “alkyl” and refers to an alkyl group substituted by a heteroaryl group, wherein the point of attachment is on the alkyl moiety. The term “unsaturated bond” refers to a double or triple bond. The term “unsaturated” or “partially unsaturated” refers to a moiety that includes at least one double or triple bond. T^{he term “saturated” or “fully saturated” refers to a moiety that does not contain a} double or triple bond, e.g., the moiety only contains single bonds. Affixing the suffix “-ene” to a group indicates the group is a divalent moiety, e.g., alkylene is the divalent moiety of alkyl, alkenylene is the divalent moiety of alkenyl, alkynylene is the divalent moiety of alkynyl, heteroalkylene is the divalent moiety of heteroalkyl, heteroalkenylene is the divalent moiety of heteroalkenyl, heteroalkynylene is the divalent moiety of heteroalkynyl, carbocyclylene is the divalent moiety of carbocyclyl, heterocyclylene is the divalent moiety of heterocyclyl, arylene is the divalent moiety of aryl, and heteroarylene is the divalent moiety of heteroaryl. A group is optionally substituted unless expressly provided otherwise. The term “optionally substituted” refers to being substituted or unsubstituted. In certain embodiments, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl groups are optionally substituted. “Optionally substituted” refers to a group which is substituted or unsubstituted (e.g., “substituted” or “unsubstituted” alkyl, “substituted” or “unsubstituted” alkenyl, “substituted” or “unsubstituted” alkynyl, “substituted” or “unsubstituted” heteroalkyl, “substituted” or “unsubstituted” heteroalkenyl, “substituted” or “unsubstituted” heteroalkynyl, “substituted” or “unsubstituted” carbocyclyl, “substituted” or “unsubstituted” heterocyclyl, “substituted” or “unsubstituted” aryl or “substituted” or “unsubstituted” heteroaryl group). In general, the term “substituted” means that at least one hydrogen present on a group is replaced with a permissible substituent, e.g., a substituent which upon substitution results in a stable compound, e.g., a compound which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, or other reaction. Unless otherwise indicated, a “substituted” group has a substituent at one or more substitutable positions of the group, and when more than one position in any given structure is substituted, the substituent is either the same or different at each position. The term “substituted” is contemplated to include substitution with all permissible substituents of organic compounds, and includes any of the substituents described herein that results in the formation of a stable compound. The present disclosure contemplates any and all such combinations in order to arrive at a stable compound. For purposes of this disclosure, heteroatoms such as nitrogen may have hydrogen substituents and/or any suitable substituent as described herein which satisfy the valencies of the heteroatoms and results in the formation of a stable moiety. The disclosure is not limited in any manner by the exemplary substituents described herein. Exemplary carbon atom substituents include halogen, −CN, −NO2, −N3, −SO2H, −SO3H, −OH, −OR^aa, −ON(R^bb)₂, −N(R^bb)₂, −N(R^bb)₃ ⁺X⁻, −N(OR^cc)R^bb, −SH, −SR^aa, −SSR^cc, −C(=O)R^aa, −CO₂H, −CHO, −C(OR^cc)₂, −CO₂R^aa, −OC(=O)R^aa, −OCO₂R^aa, −C(=O)N(R^bb)₂, −OC(=O)N(R^bb)2, −NR^bbC(=O)R^aa, −NR^bbCO2R^aa, −NR^bbC(=O)N(R^bb)2, −C(=NR^bb)R^aa, −C(=NR^bb)OR^aa, −OC(=NR^bb)R^aa, −OC(=NR^bb)OR^aa, −C(=NR^bb)N(R^bb)₂, −OC(=NR^bb)N(R^bb)₂, −NR^bbC(=NR^bb)N(R^bb)2, −C(=O)NR^bbSO2R^aa, −NR^bbSO2R^aa −OSO₂R^aa, −S(=O)R^aa, −OS(=O)R^aa, −Si(R^aa)₃, −Osi(R^aa)₃ −

−C(=S)SR^aa, −SC(=S)SR^aa, −SC(=O)SR^aa, −OC(=O)SR^aa, −SC(=O)OR^aa, −SC(=O)R^aa, −P(=O)(R^aa)2, −P(=O)(OR^cc)2, −OP(=O)(R^aa)2, −OP(=O)(OR^cc)2, −P(=O)(N(R^bb)2)2, −OP(=O)(N(R^bb)₂)₂, −NR^bbP(=O)(R^aa)₂, −NR^bbP(=O)(OR^cc)₂, −NR^bbP(=O)(N(R^bb)₂)₂, −P(R^cc)₂, −P(OR^cc)2, −P(R^cc)3⁺X⁻, −P(OR^cc)3⁺X⁻, −P(R^cc)4, −P(OR^cc)4, −OP(R^cc)2, −OP(R^cc)3⁺X⁻, −OP(OR^cc)2, −OP(OR^cc)3⁺X⁻, −OP(R^cc)4, −OP(OR^cc)4, −B(R^aa)2, −B(OR^cc)2, −BR^aa(OR^cc), C1–20 alkyl, C_1–20 perhaloalkyl, C_1–20 alkenyl, C_1–20 alkynyl, heteroC_1–20 alkyl, heteroC_1–20 alkenyl, heteroC_1–20 alkynyl, C_3-10 carbocyclyl, 3-14 membered heterocyclyl, C_6-14 aryl, and 5-14 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^dd groups; wherein X⁻ is a counterion; or two geminal hydrogens on a carbon atom are replaced with the group =O, =S, =NN(R^bb)2, =NNR^bbC(=O)R^aa, =NNR^bbC(=O)OR^aa, =NNR^bbS(=O)2R^aa, =NR^bb, or =NOR^cc; wherein: each instance of R^aa is, independently, selected from C1–20 alkyl, C1–20 perhaloalkyl, C1–20 alkenyl, C1–20 alkynyl, heteroC1–20 alkyl, heteroC1–20alkenyl, heteroC_1–20alkynyl, C_3-10 carbocyclyl, 3-14 membered heterocyclyl, C_6-14 aryl, and 5-14 membered heteroaryl, or two R^aa groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^dd groups; each instance of R^bb is, independently, selected from hydrogen, −OH, −OR^aa, −N(R^cc)₂, −CN, −C(=O)R^aa, −C(=O)N(R^cc)₂, −CO₂R^aa, −SO₂R^aa, −C(=NR^cc)OR^aa, −C(=NR^cc)N(R^cc)2, −SO2N(R^cc)2, −SO2R^cc, −SO2OR^cc, −SOR^aa, −C(=S)N(R^cc)2, −C(=O)SR^cc, −C(=S)SR^cc, −P(=O)(R^aa)2, −P(=O)(OR^cc)2, −P(=O)(N(R^cc)2)2, C1–20 alkyl, C_1–20 perhaloalkyl, C_1–20 alkenyl, C_1–20 alkynyl, heteroC_1–20alkyl, heteroC_1–20alkenyl, heteroC_1–20alkynyl, C_3-10 carbocyclyl, 3-14 membered heterocyclyl, C_6-14 aryl, and 5-14 membered heteroaryl, or two R^bb groups are joined to form a 3-14 membered h^{eterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl,} heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^dd groups; each instance of R^cc is, independently, selected from hydrogen, C1–20 alkyl, C1–20 perhaloalkyl, C_1–20 alkenyl, C_1–20 alkynyl, heteroC_1–20 alkyl, heteroC_1–20 alkenyl, heteroC1–20 alkynyl, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two R^cc groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^dd groups; each instance of R^dd is, independently, selected from halogen, −CN, −NO₂, −N₃, −SO₂H, −SO₃H, −OH, −OR^ee, −ON(R^ff)₂, −N(R^ff)₂, −N(R^ff)₃ ⁺X⁻, −N(OR^ee)R^ff, −SH, −SR^ee, −SSR^ee, −C(=O)R^ee, −CO2H, −CO2R^ee, −OC(=O)R^ee, −OCO2R^ee, −C(=O)N(R^ff)2, −OC(=O)N(R^ff)2, −NR^ffC(=O)R^ee, −NR^ffCO2R^ee, −NR^ffC(=O)N(R^ff)2, −C(=NR^ff)OR^ee, −OC(=NR^ff)R^ee, −OC(=NR^ff)OR^ee, −C(=NR^ff)N(R^ff)₂, −OC(=NR^ff)N(R^ff)₂, −NR^ffC(=NR^ff)N(R^ff)2, −NR^ffSO2R^ee, −SO2N(R^ff)2, −SO2R^ee, −SO2OR^ee, −OSO2R^ee, −S(=O)R^ee, −Si(R^ee)3, −Osi(R^ee)3, −C(=S)N(R^ff)2, −C(=O)SR^ee, −C(=S)SR^ee, −SC(=S)SR^ee, −P(=O)(OR^ee)₂, −P(=O)(R^ee)₂, −OP(=O)(R^ee)₂, −OP(=O)(OR^ee)₂, C_1–10 alkyl, C1–10 perhaloalkyl, C1–10 alkenyl, C1–10 alkynyl, heteroC1–10alkyl, heteroC1– 10alkenyl, heteroC1–10alkynyl, C3-10 carbocyclyl, 3-10 membered heterocyclyl, C6-10 aryl, and 5-10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^gg groups, or two geminal R^dd substituents are joined to form =O or =S; wherein X⁻ is a counterion; each instance of R^ee is, independently, selected from C1–10 alkyl, C1–10 perhaloalkyl, C1–10 alkenyl, C1–10 alkynyl, heteroC1–10 alkyl, heteroC1–10 alkenyl, heteroC_1–10 alkynyl, C_3-10 carbocyclyl, C_6-10 aryl, 3-10 membered heterocyclyl, and 3-10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^gg groups; each instance of R^ff is, independently, selected from hydrogen, C_1–10 alkyl, C_1–10 perhaloalkyl, C1–10 alkenyl, C1–10 alkynyl, heteroC1–10 alkyl, heteroC1–10 alkenyl, ^heteroC _1–10 ^{alkynyl, C} _3-10 ^{carbocyclyl, 3-10 membered heterocyclyl, C} _6-10 ^{aryl, and 5-10} membered heteroaryl, or two R^ff groups are joined to form a 3-10 membered heterocyclyl or 5-10 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^gg groups; each instance of R^gg is, independently, halogen, −CN, −NO2, −N3, −SO2H, −SO3H, −OH, −OC1–6 alkyl, −ON(C1–6 alkyl)2, −N(C1–6 alkyl)2, −N(C1–6 alkyl)3⁺X⁻, −NH(C1–6 alkyl)₂ ⁺X⁻, −NH₂(C_1–6 alkyl) ⁺X⁻, −NH₃ ⁺X⁻, −N(OC_1–6 alkyl)(C_1–6 alkyl), −N(OH)(C_1–6 alkyl), −NH(OH), −SH, −SC1–6 alkyl, −SS(C1–6 alkyl), −C(=O)(C1–6 alkyl), −CO2H, −CO2(C1–6 alkyl), −OC(=O)(C1–6 alkyl), −OCO2(C1–6 alkyl), −C(=O)NH2, −C(=O)N(C1–6 alkyl)₂, −OC(=O)NH(C_1–6 alkyl), −NHC(=O)( C_1–6 alkyl), −N(C_1–6 alkyl)C(=O)( C_1–6 alkyl), −NHCO₂(C_1–6 alkyl), −NHC(=O)N(C_1–6 alkyl)₂, −NHC(=O)NH(C_1–6 alkyl), −NHC(=O)NH2, −C(=NH)O(C1–6 alkyl), −OC(=NH)(C1–6 alkyl), −OC(=NH)OC1–6 alkyl, −C(=NH)N(C1–6 alkyl)2, −C(=NH)NH(C1–6 alkyl), −C(=NH)NH2, −OC(=NH)N(C_1–6 alkyl)₂, −OC(NH)NH(C_1–6 alkyl), −OC(NH)NH₂, −NHC(NH)N(C_1–6 alkyl)2, −NHC(=NH)NH2, −NHSO2(C1–6 alkyl), −SO2N(C1–6 alkyl)2, −SO2NH(C1–6 alkyl), −SO2NH2, −SO2C1–6 alkyl, −SO2OC1–6 alkyl, −OSO2C1–6 alkyl, −SOC1–6 alkyl, −Si(C_1–6 alkyl)₃, −Osi(C_1–6 alkyl)₃ −C(=S)N(C_1–6 alkyl)₂, C(=S)NH(C_1–6 alkyl), C(=S)NH2, −C(=O)S(C1–6 alkyl), −C(=S)SC1–6 alkyl, −SC(=S)SC1–6 alkyl, −P(=O)(OC1– 6 alkyl)2, −P(=O)(C1–6 alkyl)2, −OP(=O)(C1–6 alkyl)2, −OP(=O)(OC1–6 alkyl)2, C1–10 alkyl, C_1–10 perhaloalkyl, C_1–10 alkenyl, C_1–10 alkynyl, heteroC_1–10 alkyl, heteroC_1–10 alkenyl, heteroC1–10 alkynyl, C3-10 carbocyclyl, C6-10 aryl, 3-10 membered heterocyclyl, or 5-10 membered heteroaryl; or two geminal R^gg substituents can be joined to form =O or =S; and each X⁻ is a counterion. In certain embodiments, each carbon atom substituent is independently halogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C_1-6 alkyl, −OR^aa, −SR^aa, −N(R^bb)2, –CN, –SCN, –NO2, −C(=O)R^aa, −CO2R^aa, −C(=O)N(R^bb)2, −OC(=O)R^aa, −OCO2R^aa, −OC(=O)N(R^bb)2, −NR^bbC(=O)R^aa, −NR^bbCO2R^aa, or −NR^bbC(=O)N(R^bb)2. In certain embodiments, each carbon atom substituent is independently halogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C_1–10 alkyl, −OR^aa, −SR^aa, −N(R^bb)₂, – CN, –SCN, –NO2, −C(=O)R^aa, −CO2R^aa, −C(=O)N(R^bb)2, −OC(=O)R^aa, −OCO2R^aa, −OC(=O)N(R^bb)₂, −NR^bbC(=O)R^aa, −NR^bbCO₂R^aa, or −NR^bbC(=O)N(R^bb)₂, wherein R^aa is hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C_1–10 alkyl, an oxygen protecting group (e.g., silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or benzoyl) when attached to an oxygen atom, or a sulfur protecting group (e.g., acetamidomethyl, t-Bu, 3-nitro-2-pyridine sulfenyl, 2-pyridine-sulfenyl, or triphenylmethyl) when attached to a sulfur atom; and each R^bb is independently hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1–10 alkyl, or a nitrogen protecting group (e.g., Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, acetyl, or Ts). In certain embodiments, each carbon atom substituent is independently halogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1-6 alkyl, −OR^aa, −SR^aa, −N(R^bb)2, –CN, –SCN, or –NO2. In certain embodiments, each carbon atom substituent is independently halogen, substituted (e.g., substituted with one or more halogen moieties) or unsubstituted C_1–10 alkyl, −OR^aa, −SR^aa, −N(R^bb)₂, –CN, –SCN, or –NO₂, wherein R^aa is hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1–10 alkyl, an oxygen protecting group (e.g., silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or benzoyl) when attached to an oxygen atom, or a sulfur protecting group (e.g., acetamidomethyl, t-Bu, 3-nitro-2-pyridine sulfenyl, 2-pyridine-sulfenyl, or triphenylmethyl) when attached to a sulfur atom; and each R^bb is independently hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C_1–10 alkyl, or a nitrogen protecting group (e.g., Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, acetyl, or Ts). In certain embodiments, the molecular weight of a carbon atom substituent is lower than 250, lower than 200, lower than 150, lower than 100, or lower than 50 g/mol. In certain embodiments, a carbon atom substituent consists of carbon, hydrogen, fluorine, chlorine, bromine, iodine, oxygen, sulfur, nitrogen, and/or silicon atoms. In certain embodiments, a carbon atom substituent consists of carbon, hydrogen, fluorine, chlorine, bromine, iodine, oxygen, sulfur, and/or nitrogen atoms. In certain embodiments, a carbon atom substituent consists of carbon, hydrogen, fluorine, chlorine, bromine, and/or iodine atoms. In certain embodiments, a carbon atom substituent consists of carbon, hydrogen, fluorine, and/or chlorine atoms. The term “halo” or “halogen” refers to fluorine (fluoro, −F), chlorine (chloro, −Cl), bromine (bromo, −Br), or iodine (iodo, −I). The term “hydroxyl” or “hydroxy” refers to the group −OH. The term “substituted hydroxyl” or “substituted hydroxy,” by extension, refers to a hydroxyl group wherein the ^{oxygen atom directly attached to the parent molecule is substituted with a group other than} hydrogen, and includes groups selected from −OR^aa, −ON(R^bb)₂, −OC(=O)SR^aa, −OC(=O)R^aa, −OCO2R^aa, −OC(=O)N(R^bb)2, −OC(=NR^bb)R^aa, −OC(=NR^bb)OR^aa, −OC(=NR^bb)N(R^bb)2, −OS(=O)R^aa, −OSO₂R^aa, −Osi(R^aa)₃, −OP(R^cc)₂, −OP(R^cc)₃ ⁺X⁻, −OP(OR^cc)₂, −OP(OR^cc)₃ ⁺X⁻, −OP(=O)(R^aa)2, −OP(=O)(OR^cc)2, and −OP(=O)(N(R^bb))2, wherein X⁻, R^aa, R^bb, and R^cc are as defined herein. The term “alcohol” us herein, refers to an optionally substituted alkyl group, as defined herein, appended to a hydroxyl group. Representative examples of alcohol groups include but are not limited to, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, and t- butanol. The term “alkoxy” as used herein, refers to an alkyl group, as defined herein, appended to the parent molecular moiety through an oxygen atom. Representative examples of alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, 2-propoxy, butoxy and tert-butoxy. The term “thiol” or “thio” refers to the group –SH. The term “substituted thiol” or “substituted thio,” by extension, refers to a thiol group wherein the sulfur atom directly attached to the parent molecule is substituted with a group other than hydrogen, and includes groups selected from –SR^aa, –S=SR^cc, –SC(=S)SR^aa, –SC(=S)OR^aa, –SC(=S) N(R^bb)2, –SC(=O)SR^aa, – SC(=O)OR^aa, –SC(=O)N(R^bb)2, and –SC(=O)R^aa, wherein R^aa and R^cc are as defined herein. The term “amino” refers to the group −NH₂. The term “substituted amino,” by extension, refers to a monosubstituted amino, a disubstituted amino, or a trisubstituted amino. In certain embodiments, the “substituted amino” is a monosubstituted amino or a disubstituted amino group. The term “monosubstituted amino” refers to an amino group wherein the nitrogen atom directly attached to the parent molecule is substituted with one hydrogen and one group other than hydrogen, and includes groups selected from −NH(R^bb), −NHC(=O)R^aa, −NHCO₂R^aa, −NHC(=O)N(R^bb)2, −NHC(=NR^bb)N(R^bb)2, −NHSO2R^aa, −NHP(=O)(OR^cc)2, and −NHP(=O)(N(R^bb)2)2, wherein R^aa, R^bb and R^cc are as defined herein, and wherein R^bb of the group −NH(R^bb) is not hydrogen. The term “disubstituted amino” refers to an amino group wherein the nitrogen atom directly attached to the parent molecule is substituted with two groups other than hydrogen, and includes groups selected from −N(R^bb)₂, −NR^bb C(=O)R^aa, −NR^bbCO₂R^aa, −NR^bbC(=O)N(R^bb)₂, −NR^bbC(=NR^bb)N(R^bb)₂, −NR^bbSO₂R^aa, −NR^bbP(=O)(OR^cc)₂, and −NR^bbP(=O)(N(R^bb)₂)₂, wherein R^aa, R^bb, and R^cc are as defined herein, with the proviso that the nitrogen atom directly attached to the parent molecule is not substituted with hydrogen. The term “trisubstituted amino” refers to an amino group wherein the nitrogen atom directly attached to the parent molecule is substituted with three groups, and includes groups selected from −N(R^bb)₃ and −N(R^bb)₃ ⁺X⁻, wherein R^bb and X⁻ are as defined herein. The term “sulfonyl” refers to a group selected from –SO2N(R^bb)2, –SO2R^aa, and – SO₂OR^aa, wherein R^aa and R^bb are as defined herein. The term “sulfinyl” refers to the group –S(=O)R^aa, wherein R^aa is as defined herein. The term “acyl” refers to a group having the general formula −C(=O)R^X1, −C(=O)OR^X1, −C(=O)−O−C(=O)R^X1, −C(=O)SR^X1, −C(=O)N(R^X1)₂, −C(=S)R^X1, −C(=S)N(R^X1)₂, and −C(=S)S(R^X1), −C(=NR^X1)R^X1, −C(=NR^X1)OR^X1, −C(=NR^X1)SR^X1, and −C(=NR^X1)N(R^X1)2, wherein R^X1 is hydrogen; halogen; substituted or unsubstituted hydroxyl; substituted or unsubstituted thiol; substituted or unsubstituted amino; substituted or unsubstituted acyl, cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched alkyl; cyclic or acyclic, substituted or unsubstituted, branched or unbranched alkenyl; substituted or unsubstituted alkynyl; substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, aliphaticoxy, heteroaliphaticoxy, alkyloxy, heteroalkyloxy, aryloxy, heteroaryloxy, aliphaticthioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy, heteroarylthioxy, mono- or di- aliphaticamino, mono- or di- heteroaliphaticamino, mono- or di- alkylamino, mono- or di- heteroalkylamino, mono- or di-arylamino, or mono- or di-heteroarylamino; or two R^X1 groups taken together form a 5- to 6-membered heterocyclic ring. Exemplary acyl groups include aldehydes (−CHO), carboxylic acids (−CO2H), ketones, acyl halides, esters, amides, imines, carbonates, carbamates, and ureas. Acyl substituents include, but are not limited to, any of the substituents described herein, that result in the formation of a stable moiety (e.g., aliphatic, alkyl, alkenyl, alkynyl, heteroaliphatic, heterocyclic, aryl, heteroaryl, acyl, oxo, imino, thiooxo, cyano, isocyano, amino, azido, nitro, hydroxyl, thiol, halo, aliphaticamino, heteroaliphaticamino, alkylamino, heteroalkylamino, arylamino, heteroarylamino, alkylaryl, arylalkyl, aliphaticoxy, heteroaliphaticoxy, alkyloxy, heteroalkyloxy, aryloxy, heteroaryloxy, aliphaticthioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy, heteroarylthioxy, acyloxy, and the like, each of which may or may not be further substituted). The term “carbonyl” refers to a group wherein the carbon directly attached to the parent molecule is sp² hybridized, and is substituted with an oxygen, nitrogen or sulfur atom, e.g., a ^{group selected from ketones (–C(=O)Raa), carboxylic acids (–CO} ₂ ^{H), aldehydes (–CHO), esters} (–CO₂R^aa, –C(=O)SR^aa, –C(=S)SR^aa), amides (–C(=O)N(R^bb)₂, –C(=O)NR^bbSO₂R^aa, −C(=S)N(R^bb)2), and imines (–C(=NR^bb)R^aa, –C(=NR^bb)OR^aa), –C(=NR^bb)N(R^bb)2), wherein R^aa and R^bb are as defined herein. Nitrogen atoms can be substituted or unsubstituted as valency permits, and include primary, secondary, tertiary, and quaternary nitrogen atoms. Exemplary nitrogen atom substituents include hydrogen, −OH, −OR^aa, −N(R^cc)2, −CN, −C(=O)R^aa, −C(=O)N(R^cc)2,

−SO₂OR^cc, −SOR^aa, −C(=S)N(R^cc)₂, −C(=O)SR^cc, −C(=S)SR^cc, −P(=O)(OR^cc)₂, −P(=O)(R^aa)₂, −P(=O)(N(R^cc)2)2, C1–20 alkyl, C1–20 perhaloalkyl, C1–20 alkenyl, C1–20 alkynyl, hetero C1–20 alkyl, hetero C1–20 alkenyl, hetero C1–20 alkynyl, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two R^cc groups attached to an N atom are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^dd groups, and wherein R^aa, R^bb, R^cc and R^dd are as defined above. In certain embodiments, each nitrogen atom substituent is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-6 alkyl, −C(=O)R^aa, −CO2R^aa, −C(=O)N(R^bb)₂, or a nitrogen protecting group. In certain embodiments, each nitrogen atom substituent is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-10 alkyl, −C(=O)R^aa, −CO2R^aa, −C(=O)N(R^bb)2, or a nitrogen protecting group, wherein R^aa is hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1-10 alkyl, or an oxygen protecting group when attached to an oxygen atom; and each R^bb is independently hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C_1-10 alkyl, or a nitrogen protecting group. In certain embodiments, each nitrogen atom substituent is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-6 alkyl or a nitrogen protecting group. In certain embodiments, the substituent present on the nitrogen atom is a nitrogen protecting group (also referred to herein as an “amino protecting group”). Nitrogen protecting groups include −OH, −OR^aa, −N(R^cc)2, −C(=O)R^aa, −C(=O)N(R^cc)2, −CO2R^aa, −SO2R^aa, −C(=NR^cc)R^aa, −C(=NR^cc)OR^aa, −C(=NR^cc)N(R^cc)₂, −SO₂N(R^cc)₂, −SO₂R^cc, −SO₂OR^cc, −SOR^aa, −C(=S)N(R^cc)₂, −C(=O)SR^cc, −C(=S)SR^cc, C_1–10 alkyl (e.g., aralkyl, heteroaralkyl), C_1–20 alkenyl, C1–20 alkynyl, hetero C1–20 alkyl, hetero C1–20 alkenyl, hetero C1–20 alkynyl, C3-10 ^{carbocyclyl, 3-14 membered heterocyclyl, C} _6-14 ^{aryl, and 5-14 membered heteroaryl groups,} wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aralkyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^dd groups, and wherein R^aa, R^bb, R^cc and R^dd are as defined herein. Nitrogen protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3^rd edition, John Wiley & Sons, 1999, incorporated herein by reference. For example, in certain embodiments, at least one nitrogen protecting group is an amide group (e.g., a moiety that include the nitrogen atom to which the nitrogen protecting groups (e.g., −C(=O)R^aa) is directly attached). In certain such embodiments, each nitrogen protecting group, together with the nitrogen atom to which the nitrogen protecting group is attached, is independently selected from the group consisting of formamide, acetamide, chloroacetamide, trichloroacetamide, trifluoroacetamide, phenylacetamide, 3-phenylpropanamide, picolinamide, 3-pyridylcarboxamide, N-benzoylphenylalanyl derivatives, benzamide, p-phenylbenzamide, o- nitophenylacetamide, o-nitrophenoxyacetamide, acetoacetamide, (N’- dithiobenzyloxyacylamino)acetamide, 3-(p-hydroxyphenyl)propanamide, 3-(o- nitrophenyl)propanamide, 2-methyl-2-(o-nitrophenoxy)propanamide, 2-methyl-2-(o- phenylazophenoxy)propanamide, 4-chlorobutanamide, 3-methyl-3-nitrobutanamide, o- nitrocinnamide, N-acetylmethionine derivatives, o-nitrobenzamide, and o- (benzoyloxymethyl)benzamide. In certain embodiments, at least one nitrogen protecting group is a carbamate group (e.g., a moiety that include the nitrogen atom to which the nitrogen protecting groups (e.g., −C(=O)OR^aa) is directly attached). In certain such embodiments, each nitrogen protecting group, together with the nitrogen atom to which the nitrogen protecting group is attached, is independently selected from the group consisting of methyl carbamate, ethyl carbamate, 9- fluorenylmethyl carbamate (Fmoc), 9-(2-sulfo)fluorenylmethyl carbamate, 9-(2,7- dibromo)fluoroenylmethyl carbamate, 2,7-di-t-butyl-[9-(10,10-dioxo-10,10,10,10- tetrahydrothioxanthyl)]methyl carbamate (DBD-Tmoc), 4-methoxyphenacyl carbamate (Phenoc), 2,2,2-trichloroethyl carbamate (Troc), 2-trimethylsilylethyl carbamate (Teoc), 2- phenylethyl carbamate (hZ), 1–(1-adamantyl)-1-methylethyl carbamate (Adpoc), 1,1-dimethyl- 2-haloethyl carbamate, 1,1-dimethyl-2,2-dibromoethyl carbamate (DB-t-BOC), 1,1-dimethyl- 2,2,2-trichloroethyl carbamate (TCBOC), 1-methyl-1-(4-biphenylyl)ethyl carbamate (Bpoc), 1- (3,5-di-t-butylphenyl)-1-methylethyl carbamate (t-Bumeoc), 2-(2¢- and 4¢-pyridyl)ethyl carbamate (Pyoc), 2-(N,N-dicyclohexylcarboxamido)ethyl carbamate, t-butyl carbamate (BOC or Boc), 1-adamantyl carbamate (Adoc), vinyl carbamate (Voc), allyl carbamate (Alloc), 1- isopropylallyl carbamate (Ipaoc), cinnamyl carbamate (Coc), 4-nitrocinnamyl carbamate (Noc), 8-quinolyl carbamate, N-hydroxypiperidinyl carbamate, alkyldithio carbamate, benzyl carbamate (Cbz), p-methoxybenzyl carbamate (Moz), p-nitobenzyl carbamate, p-bromobenzyl carbamate, p-chlorobenzyl carbamate, 2,4-dichlorobenzyl carbamate, 4-methylsulfinylbenzyl carbamate (Msz), 9-anthrylmethyl carbamate, diphenylmethyl carbamate, 2-methylthioethyl carbamate, 2-methylsulfonylethyl carbamate, 2-(p-toluenesulfonyl)ethyl carbamate, [2-(1,3- dithianyl)]methyl carbamate (Dmoc), 4-methylthiophenyl carbamate (Mtpc), 2,4- dimethylthiophenyl carbamate (Bmpc), 2-phosphonioethyl carbamate (Peoc), 2- triphenylphosphonioisopropyl carbamate (Ppoc), 1,1-dimethyl-2-cyanoethyl carbamate, m- chloro-p-acyloxybenzyl carbamate, p-(dihydroxyboryl)benzyl carbamate, 5- benzisoxazolylmethyl carbamate, 2-(trifluoromethyl)-6-chromonylmethyl carbamate (Tcroc), m- nitrophenyl carbamate, 3,5-dimethoxybenzyl carbamate, o-nitrobenzyl carbamate, 3,4- dimethoxy-6-nitrobenzyl carbamate, phenyl(o-nitrophenyl)methyl carbamate, t-amyl carbamate, S-benzyl thiocarbamate, p-cyanobenzyl carbamate, cyclobutyl carbamate, cyclohexyl carbamate, cyclopentyl carbamate, cyclopropylmethyl carbamate, p-decyloxybenzyl carbamate, 2,2- dimethoxyacylvinyl carbamate, o-(N,N-dimethylcarboxamido)benzyl carbamate, 1,1-dimethyl- 3-(N,N-dimethylcarboxamido)propyl carbamate, 1,1-dimethylpropynyl carbamate, di(2- pyridyl)methyl carbamate, 2-furanylmethyl carbamate, 2-iodoethyl carbamate, isoborynl carbamate, isobutyl carbamate, isonicotinyl carbamate, p-(p’-methoxyphenylazo)benzyl carbamate, 1-methylcyclobutyl carbamate, 1-methylcyclohexyl carbamate, 1-methyl-1- cyclopropylmethyl carbamate, 1-methyl-1-(3,5-dimethoxyphenyl)ethyl carbamate, 1-methyl-1- (p-phenylazophenyl)ethyl carbamate, 1-methyl-1-phenylethyl carbamate, 1-methyl-1-(4- pyridyl)ethyl carbamate, phenyl carbamate, p-(phenylazo)benzyl carbamate, 2,4,6-tri-t- butylphenyl carbamate, 4-(trimethylammonium)benzyl carbamate, and 2,4,6-trimethylbenzyl carbamate. In certain embodiments, at least one nitrogen protecting group is a sulfonamide group (e.g., a moiety that include the nitrogen atom to which the nitrogen protecting groups (e.g., −S(=O)2R^aa) is directly attached). In certain such embodiments, each nitrogen protecting group, together with the nitrogen atom to which the nitrogen protecting group is attached, is independently selected from the group consisting of p-toluenesulfonamide (Ts), benzenesulfonamide, 2,3,6-trimethyl-4-methoxybenzenesulfonamide (Mtr), 2,4,6- ^{trimethoxybenzenesulfonamide (Mtb), 2,6-dimethyl-4-methoxybenzenesulfonamide (Pme),} 2,3,5,6-tetramethyl-4-methoxybenzenesulfonamide (Mte), 4-methoxybenzenesulfonamide (Mbs), 2,4,6-trimethylbenzenesulfonamide (Mts), 2,6-dimethoxy-4-methylbenzenesulfonamide (iMds), 2,2,5,7,8-pentamethylchroman-6-sulfonamide (Pmc), methanesulfonamide (Ms), β- trimethylsilylethanesulfonamide (SES), 9-anthracenesulfonamide, 4-(4¢,8¢- dimethoxynaphthylmethyl)benzenesulfonamide (DNMBS), benzylsulfonamide, trifluoromethylsulfonamide, and phenacylsulfonamide. In certain embodiments, each nitrogen protecting group, together with the nitrogen atom to which the nitrogen protecting group is attached, is independently selected from the group consisting of phenothiazinyl-(10)-acyl derivatives, N’-p-toluenesulfonylaminoacyl derivatives, N’-phenylaminothioacyl derivatives, N-benzoylphenylalanyl derivatives, N-acetylmethionine derivatives, 4,5-diphenyl-3-oxazolin-2-one, N-phthalimide, N-dithiasuccinimide (Dts), N-2,3- diphenylmaleimide, N-2,5-dimethylpyrrole, N-1,1,4,4-tetramethyldisilylazacyclopentane adduct (STABASE), 5-substituted 1,3-dimethyl-1,3,5-triazacyclohexan-2-one, 5-substituted 1,3- dibenzyl-1,3,5-triazacyclohexan-2-one, 1-substituted 3,5-dinitro-4-pyridone, N-methylamine, N- allylamine, N-[2-(trimethylsilyl)ethoxy]methylamine (SEM), N-3-acetoxypropylamine, N-(1- isopropyl-4-nitro-2-oxo-3-pyroolin-3-yl)amine, quaternary ammonium salts, N-benzylamine, N- di(4-methoxyphenyl)methylamine, N-5-dibenzosuberylamine, N-triphenylmethylamine (Tr), N- [(4-methoxyphenyl)diphenylmethyl]amine (MMTr), N-9-phenylfluorenylamine (PhF), N-2,7- dichloro-9-fluorenylmethyleneamine, N-ferrocenylmethylamino (Fcm), N-2-picolylamino N’- oxide, N-1,1-dimethylthiomethyleneamine, N-benzylideneamine, N-p- methoxybenzylideneamine, N-diphenylmethyleneamine, N-[(2-pyridyl)mesityl]methyleneamine, N-(N’,N’-dimethylaminomethylene)amine, N-p-nitrobenzylideneamine, N-salicylideneamine, N- 5-chlorosalicylideneamine, N-(5-chloro-2-hydroxyphenyl)phenylmethyleneamine, N- cyclohexylideneamine, N-(5,5-dimethyl-3-oxo-1-cyclohexenyl)amine, N-borane derivatives, N- diphenylborinic acid derivatives, N-[phenyl(pentaacylchromium- or tungsten)acyl]amine, N- copper chelate, N-zinc chelate, N-nitroamine, N-nitrosoamine, amine N-oxide, diphenylphosphinamide (Dpp), dimethylthiophosphinamide (Mpt), diphenylthiophosphinamide (Ppt), dialkyl phosphoramidates, dibenzyl phosphoramidate, diphenyl phosphoramidate, benzenesulfenamide, o-nitrobenzenesulfenamide (Nps), 2,4-dinitrobenzenesulfenamide, pentachlorobenzenesulfenamide, 2-nitro-4-methoxybenzenesulfenamide, triphenylmethylsulfenamide, and 3-nitropyridinesulfenamide (Npys). In some embodiments, two instances of a nitrogen protecting group together with the nitrogen atoms to which the nitrogen protecting groups are attached are N,N’-isopropylidenediamine. In certain embodiments, at least one nitrogen protecting group is Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, acetyl, or Ts. In certain embodiments, each oxygen atom substituent is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C_1-10 alkyl, −C(=O)R^aa, −CO₂R^aa, −C(=O)N(R^bb)2, or an oxygen protecting group. In certain embodiments, each oxygen atom substituents is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C_1-6 alkyl, −C(=O)R^aa, −CO₂R^aa, −C(=O)N(R^bb)₂, or an oxygen protecting group, wherein R^aa is hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1-10 alkyl, or an oxygen protecting group when attached to an oxygen atom; and each R^bb is independently hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C_1-10 alkyl, or a nitrogen protecting group. In certain embodiments, each oxygen atom substituent is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-6 alkyl or an oxygen protecting group. In certain embodiments, the substituent present on an oxygen atom is an oxygen protecting group (also referred to herein as an “hydroxyl protecting group”). Oxygen protecting groups include −R^aa, −N(R^bb)2, −C(=O)SR^aa, −C(=O)R^aa, −CO2R^aa, −C(=O)N(R^bb)2, −C(=NR^bb)R^aa, −C(=NR^bb)OR^aa, −C(=NR^bb)N(R^bb)₂, −S(=O)R^aa, −SO₂R^aa, −Si(R^aa)₃, −P(R^cc)₂, −P(R^cc)3⁺X⁻, −P(OR^cc)2, −P(OR^cc)3⁺X⁻, −P(=O)(R^aa)2, −P(=O)(OR^cc)2, and −P(=O)(N(R^bb) 2)2, wherein X⁻, R^aa, R^bb, and R^cc are as defined herein. Oxygen protecting groups are well known in the art and include those described In detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3^rd edition, John Wiley & Sons, 1999, incorporated herein by reference. In certain embodiments, each oxygen protecting group, together with the oxygen atom to which the oxygen protecting group is attached, is selected from the group consisting of methyl, methoxymethyl (MOM), methylthiomethyl (MTM), t-butylthiomethyl, (phenyldimethylsilyl)methoxymethyl (SMOM), benzyloxymethyl (BOM), p- methoxybenzyloxymethyl (PMBM), (4-methoxyphenoxy)methyl (p-AOM), guaiacolmethyl (GUM), t-butoxymethyl, 4-pentenyloxymethyl (POM), siloxymethyl, 2-methoxyethoxymethyl (MEM), 2,2,2-trichloroethoxymethyl, bis(2-chloroethoxy)methyl, 2- (trimethylsilyl)ethoxymethyl (SEMOR), tetrahydropyranyl (THP), 3-bromotetrahydropyranyl, tetrahydrothiopyranyl, 1-methoxycyclohexyl, 4-methoxytetrahydropyranyl (MTHP), 4- ^{methoxytetrahydrothiopyranyl, 4-methoxytetrahydrothiopyranyl S,S-dioxide, 1-[(2-chloro-4-} methyl)phenyl]-4-methoxypiperidin-4-yl (CTMP), 1,4-dioxan-2-yl, tetrahydrofuranyl, tetrahydrothiofuranyl, 2,3,3a,4,5,6,7,7a-octahydro-7,8,8-trimethyl-4,7-methanobenzofuran-2-yl, 1-ethoxyethyl, 1-(2-chloroethoxy)ethyl, 1-methyl-1-methoxyethyl, 1-methyl-1-benzyloxyethyl, 1-methyl-1-benzyloxy-2-fluoroethyl, 2,2,2-trichloroethyl, 2-trimethylsilylethyl, 2- (phenylselenyl)ethyl, t-butyl, allyl, p-chlorophenyl, p-methoxyphenyl, 2,4-dinitrophenyl, benzyl (Bn), p-methoxybenzyl (PMB), 3,4-dimethoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, p- halobenzyl, 2,6-dichlorobenzyl, p-cyanobenzyl, p-phenylbenzyl, 2-picolyl, 4-picolyl, 3-methyl- 2-picolyl N-oxido, diphenylmethyl, p,p’-dinitrobenzhydryl, 5-dibenzosuberyl, triphenylmethyl, 4,4′-dimethoxytrityl (4,4′-dimethoxytriphenylmethyl or DMT), α-naphthyldiphenylmethyl, p- methoxyphenyldiphenylmethyl, di(p-methoxyphenyl)phenylmethyl, tri(p- methoxyphenyl)methyl, 4-(4’-bromophenacyloxyphenyl)diphenylmethyl, 4,4′,4″-tris(4,5- dichlorophthalimidophenyl)methyl, 4,4′,4″-tris(levulinoyloxyphenyl)methyl, 4,4′,4″- tris(benzoyloxyphenyl)methyl, 4,4’-Dimethoxy-”"‘-[N-(imidazolylmethyl) ]trityl Ether (IDTr- OR), 4,4’-Dimethoxy-”"‘-[N-(imidazolylethyl)carbamoyl]trityl Ether (IETr-OR), 1,1-bis(4- methoxyphenyl)-1′-pyrenylmethyl, 9-anthryl, 9-(9-phenyl)xanthenyl, 9-(9-phenyl-10- oxo)anthryl, 1,3-benzodithiolan-2-yl, benzisothiazolyl S,S-dioxido, trimethylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), dimethylisopropylsilyl (IPDMS), diethylisopropylsilyl (DEIPS), dimethylthexylsilyl, t-butyldimethylsilyl (TBDMS), t- butyldiphenylsilyl (TBDPS), tribenzylsilyl, tri-p-xylylsilyl, triphenylsilyl, diphenylmethylsilyl (DPMS), t-butylmethoxyphenylsilyl (TBMPS), formate, benzoylformate, acetate, chloroacetate, dichloroacetate, trichloroacetate, trifluoroacetate, methoxyacetate, triphenylmethoxyacetate, phenoxyacetate, p-chlorophenoxyacetate, 3-phenylpropionate, 4-oxopentanoate (levulinate), 4,4- (ethylenedithio)pentanoate (levulinoyldithioacetal), pivaloate, adamantoate, crotonate, 4- methoxycrotonate, benzoate, p-phenylbenzoate, 2,4,6-trimethylbenzoate (mesitoate), methyl carbonate, 9-fluorenylmethyl carbonate (Fmoc), ethyl carbonate, 2,2,2-trichloroethyl carbonate (Troc), 2-(trimethylsilyl)ethyl carbonate (TMSEC), 2-(phenylsulfonyl) ethyl carbonate (Psec), 2- (triphenylphosphonio) ethyl carbonate (Peoc), isobutyl carbonate, vinyl carbonate, allyl carbonate, t-butyl carbonate (BOC or Boc), p-nitrophenyl carbonate, benzyl carbonate, p- methoxybenzyl carbonate, 3,4-dimethoxybenzyl carbonate, o-nitrobenzyl carbonate, p- nitrobenzyl carbonate, S-benzyl thiocarbonate, 4-ethoxy-1-napththyl carbonate, methyl dithiocarbonate, 2-iodobenzoate, 4-azidobutyrate, 4-nitro-4-methylpentanoate, o- (dibromomethyl)benzoate, 2-formylbenzenesulfonate, 2-(methylthiomethoxy)ethyl carbonate ^{(MTMEC-OR), 4-(methylthiomethoxy)butyrate, 2-(methylthiomethoxymethyl)benzoate, 2,6-} dichloro-4-methylphenoxyacetate, 2,6-dichloro-4-(1,1,3,3-tetramethylbutyl)phenoxyacetate, 2,4- bis(1,1-dimethylpropyl)phenoxyacetate, chlorodiphenylacetate, isobutyrate, monosuccinoate, (E)-2-methyl-2-butenoate, o-(methoxyacyl)benzoate, α-naphthoate, nitrate, alkyl N,N,N’,N’- tetramethylphosphorodiamidate, alkyl N-phenylcarbamate, borate, dimethylphosphinothioyl, alkyl 2,4-dinitrophenylsulfenate, sulfate, methanesulfonate (mesylate), benzylsulfonate, and tosylate (Ts). In certain embodiments, at least one oxygen protecting group is silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or benzoyl. In certain embodiments, each sulfur atom substituent is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-10 alkyl, −C(=O)R^aa, −CO2R^aa, −C(=O)N(R^bb)₂, or a sulfur protecting group. In certain embodiments, each sulfur atom substituent is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-10 alkyl, −C(=O)R^aa, −CO2R^aa, −C(=O)N(R^bb)2, or a sulfur protecting group, wherein R^aa is hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C_1-10 alkyl, or an oxygen protecting group when attached to an oxygen atom; and each R^bb is independently hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1-10 alkyl, or a nitrogen protecting group. In certain embodiments, each sulfur atom substituent is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-6 alkyl or a sulfur protecting group. In certain embodiments, the substituent present on a sulfur atom is a sulfur protecting group (also referred to as a “thiol protecting group”). In some embodiments, each sulfur protecting group is selected from the group consisting of −R^aa, −N(R^bb)2, −C(=O)SR^aa, −C(=O)R^aa, −CO2R^aa, −C(=O)N(R^bb)2, −C(=NR^bb)R^aa, −C(=NR^bb)OR^aa, −C(=NR^bb)N(R^bb)2, −S(=O)R^aa, −SO₂R^aa, −Si(R^aa)₃, −P(R^cc)₂, −P(R^cc)₃ ⁺X⁻, −P(OR^cc)₂, −P(OR^cc)₃ ⁺X⁻, −P(=O)(R^aa)₂, −P(=O)(OR^cc)2, and −P(=O)(N(R^bb) 2)2, wherein R^aa, R^bb, and R^cc are as defined herein. Sulfur protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3^rd edition, John Wiley & Sons, 1999, incorporated herein by reference. In certain embodiments, the molecular weight of a substituent is lower than 250, lower than 200, lower than 150, lower than 100, or lower than 50 g/mol. In certain embodiments, a substituent consists of carbon, hydrogen, fluorine, chlorine, bromine, iodine, oxygen, sulfur, nitrogen, and/or silicon atoms. In certain embodiments, a substituent consists of carbon, ^{hydrogen, fluorine, chlorine, bromine, iodine, oxygen, sulfur, and/or nitrogen atoms. In certain} embodiments, a substituent consists of carbon, hydrogen, fluorine, chlorine, bromine, and/or iodine atoms. In certain embodiments, a substituent consists of carbon, hydrogen, fluorine, and/or chlorine atoms. In certain embodiments, a substituent comprises 0, 1, 2, or 3 hydrogen bond donors. In certain embodiments, a substituent comprises 0, 1, 2, or 3 hydrogen bond acceptors. A “counterion” or “anionic counterion” is a negatively charged group associated with a positively charged group in order to maintain electronic neutrality. An anionic counterion may be monovalent (e.g., including one formal negative charge). An anionic counterion may also be multivalent (e.g., including more than one formal negative charge), such as divalent or trivalent. Exemplary counterions include halide ions (e.g., F^–, Cl^–, Br^–, I^–), NO3^–, ClO4^–, OH^–, H2PO4^–, HCO₃− _, HSO₄ ^–, sulfonate ions (e.g., methanesulfonate, trifluoromethanesulfonate, p– toluenesulfonate, benzenesulfonate, 10–camphor sulfonate, naphthalene–2–sulfonate, naphthalene–1–sulfonic acid–5–sulfonate, ethan–1–sulfonic acid–2–sulfonate, and the like), carboxylate ions (e.g., acetate, propanoate, benzoate, glycerate, lactate, tartrate, glycolate, gluconate, and the like), BF₄ ⁻, PF₄ ^–, PF₆ ^–, AsF₆ ^–, SbF₆ ^–, B[3,5-(CF₃)₂C₆H₃]₄]^–, B(C₆F₅)₄ ⁻, BPh₄ ^–, Al(OC(CF3)3)4^–, and carborane anions (e.g., CB11H12^– or (HCB11Me5Br6)^–). Exemplary counterions which may be multivalent include CO3²⁻, HPO4²⁻, PO 3− 4 , B4O7²⁻, SO4²⁻, S2O3²⁻, carboxylate anions (e.g., tartrate, citrate, fumarate, maleate, malate, malonate, gluconate, succinate, glutarate, adipate, pimelate, suberate, azelate, sebacate, salicylate, phthalates, aspartate, glutamate, and the like), and carboranes. A “leaving group” (LG) is an art-understood term referring to an atomic or molecular fragment that departs with a pair of electrons in heterolytic bond cleavage, wherein the molecular fragment is an anion or neutral molecule. As used herein, a leaving group can be an atom or a group capable of being displaced by a nucleophile. See e.g., Smith, March Advanced Organic Chemistry ^6th ed. (501–502). Exemplary leaving groups include, but are not limited to, halo (e.g., fluoro, chloro, bromo, iodo) and activated substituted hydroxyl groups (e.g., – OC(=O)SR^aa, –OC(=O)R^aa, –OCO₂R^aa, –OC(=O)N(R^bb)₂, –OC(=NR^bb)R^aa, –OC(=NR^bb)OR^aa, – OC(=NR^bb)N(R^bb)2, –OS(=O)R^aa, –OSO2R^aa, –OP(R^cc)2, –OP(R^cc)3, –OP(=O)2R^aa, – OP(=O)(R^aa)2, –OP(=O)(OR^cc)2, –OP(=O)2N(R^bb)2, and –OP(=O)(NR^bb)2, wherein R^aa, R^bb, and R^cc are as defined herein). Additional examples of suitable leaving groups include, but are not limited to, halogen alkoxycarbonyloxy, aryloxycarbonyloxy, alkanesulfonyloxy, arenesulfonyloxy, alkyl-carbonyloxy (e.g., acetoxy), arylcarbonyloxy, aryloxy, methoxy, N,O- ^{dimethylhydroxylamino, pixyl, and haloformates. In some embodiments, the leaving group is a} sulfonic acid ester, such as toluenesulfonate (tosylate, –oTs), methanesulfonate (mesylate, – oMs), p-bromobenzenesulfonyloxy (brosylate, –oBs), –OS(=O)2(CF2)3CF3 (nonaflate, –oNf), or trifluoromethanesulfonate (triflate, –oTf). In some embodiments, the leaving group is a brosylate, such as p-bromobenzenesulfonyloxy. In some embodiments, the leaving group is a nosylate, such as 2-nitrobenzenesulfonyloxy. In some embodiments, the leaving group is a sulfonate-containing group. In some embodiments, the leaving group is a tosylate group. In some embodiments, the leaving group is a phosphineoxide (e.g., formed during a Mitsunobu reaction) or an internal leaving group such as an epoxide or cyclic sulfate. Other non-limiting examples of leaving groups are water, ammonia, alcohols, ether moieties, thioether moieties, zinc halides, magnesium moieties, diazonium salts, and copper moieties. Use of the phrase “at least one instance” refers to 1, 2, 3, 4, or more instances, but also encompasses a range, e.g., for example, from 1 to 4, from 1 to 3, from 1 to 2, from 2 to 4, from 2 to 3, or from 3 to 4 instances, inclusive. A “non-hydrogen group” refers to any group that is defined for a particular variable that is not hydrogen. These and other exemplary substituents are described in more detail in the Detailed Description, Examples, and Claims. The present disclosure is not limited in any manner by the above exemplary listing of substituents. The following definitions are more general terms used throughout the present application. As used herein, the term “salt” refers to any and all salts, and encompasses pharmaceutically acceptable salts. Salts include ionic compounds that result from the neutralization reaction of an acid and a base. A salt is composed of one or more cations (positively charged ions) and one or more anions (negative ions) so that the salt is electrically neutral (without a net charge). Salts of the compounds of the present disclosure include those derived from inorganic and organic acids and bases. Examples of acid addition salts are salts of an amino group formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid, or with organic acids, such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid or by using other methods known in the art such as ion exchange. Other salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, ^{hexanoate, hydroiodide, 2–hydroxy–ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate,} malate, maleate, malonate, methanesulfonate, 2–naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3–phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, hippurate, and the like. Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and N⁺(C_1–4 alkyl)₄ salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further salts include ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate. The term “pharmaceutically acceptable salt” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1-19, incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of the present disclosure include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid or with organic acids, such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid or by using other methods known in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like. Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium, and N⁺(C_1-4 alkyl)₄ salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further ^{pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary} ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate. The term “solvate” refers to forms of the compound, or a salt thereof, that are associated with a solvent, usually by a solvolysis reaction. This physical association may include hydrogen bonding. Conventional solvents include water, methanol, ethanol, acetic acid, DMSO, THF, diethyl ether, and the like. The compounds described herein may be prepared, e.g., in crystalline form, and may be solvated. Suitable solvates include pharmaceutically acceptable solvates and further include both stoichiometric solvates and non-stoichiometric solvates. In certain instances, the solvate will be capable of isolation, for example, when one or more solvent molecules are incorporated in the crystal lattice of a crystalline solid. “Solvate” encompasses both solution-phase and isolatable solvates. Representative solvates include hydrates, ethanolates, and methanolates. The term “stoichiometric solvate” refers to a solvate, which comprises a compound (e.g., a compound disclosed herein) and a solvent, wherein the solvent molecules are an integral part of the crystal lattice, in which they interact strongly with the compound and each other. The removal of the solvent molecules will cause instability of the crystal network, which subsequently collapses into an amorphous phase or recrystallizes as a new crystalline form with reduced solvent content. The term “non-stoichiometric solvate” refers to a solvate, which comprises a compound (e.g., a compound disclosed herein) and a solvent, wherein the solvent content may vary without major changes in the crystal structure. The amount of solvent in the crystal lattice only depends on the partial pressure of solvent in the surrounding atmosphere. In the fully solvated state, non- stoichiometric solvates may, but not necessarily have to, show an integer molar ratio of solvent to the compound. During drying of a non-stoichiometric solvate, a portion of the solvent may be removed without significantly disturbing the crystal network, and the resulting solvate can subsequently be resolvated to give the initial crystalline form. Unlike stoichiometric solvates, the desolvation and resolvation of non-stoichiometric solvates is not accompanied by a phase transition, and all solvation states represent the same crystal form. The term “hydrate” refers to a compound that is associated with water. Typically, the number of the water molecules contained in a hydrate of a compound is in a definite ratio to the number of the compound molecules in the hydrate. Therefore, a hydrate of a compound may be represented, for example, by the general formula R×x H₂O, wherein R is the compound, and x is a number greater than 0. A given compound may form more than one type of hydrate, including, e.g., monohydrates (x is 1), lower hydrates (x is a number greater than 0 and smaller than 1, e.g., hemihydrates (R×0.5 H2O)), and polyhydrates (x is a number greater than 1, e.g., dihydrates (R×2 H2O) and hexahydrates (R×6 H2O)). The term “tautomers” or “tautomeric” refers to two or more interconvertible compounds resulting from at least one formal migration of a hydrogen atom and at least one change in valency (e.g., a single bond to a double bond, a triple bond to a single bond, or vice versa). The exact ratio of the tautomers depends on several factors, including temperature, solvent, and pH. Tautomerizations (i.e., the reaction providing a tautomeric pair) may catalyzed by acid or base. Exemplary tautomerizations include keto-to-enol, amide-to-imide, lactam-to-lactim, enamine-to- imine, and enamine-to-(a different enamine) tautomerizations. It is also to be understood that compounds that have the same molecular formula but differ in the nature or sequence of bonding of their atoms or the arrangement of their atoms in space are termed “isomers”. Isomers that differ in the arrangement of their atoms in space are termed “stereoisomers”. Stereoisomers that are not mirror images of one another are termed “diastereomers” and those that are non-superimposable mirror images of each other are termed “enantiomers”. When a compound has an asymmetric center, for example, it is bonded to four different groups, a pair of enantiomers is possible. An enantiomer can be characterized by the absolute configuration of its asymmetric center and is described by the R- and S-sequencing rules of Cahn and Prelog, or by the manner in which the molecule rotates the plane of polarized light and designated as dextrorotatory or levorotatory (i.e., as (+) or (−)-isomers respectively). A chiral compound can exist as either individual enantiomer or as a mixture thereof. A mixture containing equal proportions of the enantiomers is called a “racemic mixture”. The term “crystalline” or “crystalline form” refers to a solid form substantially exhibiting three-dimensional order. In certain embodiments, a crystalline form of a solid is a solid form that is substantially not amorphous. In certain embodiments, the X-ray powder diffraction (XRPD) pattern of a crystalline form includes one or more sharply defined peaks. The term “amorphous” or “amorphous form” refers to a form of a solid (“solid form”), the form substantially lacking three-dimensional order. In certain embodiments, an amorphous form of a solid is a solid form that is substantially not crystalline. In certain embodiments, the X- ray powder diffraction (XRPD) pattern of an amorphous form includes a wide scattering band with a peak at 2θ of, e.g., between 20 and 70°, inclusive, using CuKα radiation. In certain embodiments, the XRPD pattern of an amorphous form further includes one or more peaks attributed to crystalline structures. In certain embodiments, the maximum intensity of any one of the one or more peaks attributed to crystalline structures observed at a 2θ of between 20 and 70°, inclusive, is not more than 300-fold, not more than 100-fold, not more than 30-fold, not more than 10-fold, or not more than 3-fold of the maximum intensity of the wide scattering band. In certain embodiments, the XRPD pattern of an amorphous form includes no peaks attributed to crystalline structures. The term “co-crystal” refers to a crystalline structure comprising at least two different components (e.g., a compound disclosed herein and an acid), wherein each of the components is independently an atom, ion, or molecule. In certain embodiments, none of the components is a solvent. In certain embodiments, at least one of the components is a solvent. A co-crystal of a compound disclosed herein and an acid is different from a salt formed from a compound disclosed herein and the acid. In the salt, a compound disclosed herein is complexed with the acid in a way that proton transfer (e.g., a complete proton transfer) from the acid to a compound disclosed herein easily occurs at room temperature. In the co-crystal, however, a compound disclosed herein is complexed with the acid in a way that proton transfer from the acid to a compound disclosed herein does not easily occur at room temperature. In certain embodiments, in the co-crystal, there is no proton transfer from the acid to a compound disclosed herein. In certain embodiments, in the co-crystal, there is partial proton transfer from the acid to a compound disclosed herein. Co-crystals may be useful to improve the properties (e.g., solubility, stability, and ease of formulation) of a compound disclosed herein. The term “polymorph” refers to a crystalline form of a compound (or a salt, hydrate, or solvate thereof). All polymorphs have the same elemental composition. Different crystalline forms usually have different X-ray diffraction patterns, infrared spectra, melting points, density, hardness, crystal shape, optical and electrical properties, stability, and solubility. Recrystallization solvent, rate of crystallization, storage temperature, and other factors may cause one crystal form to dominate. Various polymorphs of a compound can be prepared by crystallization under different conditions. The term “prodrugs” refers to compounds that have cleavable groups and become by solvolysis or under physiological conditions the compounds described herein, which are pharmaceutically active in vivo. Such examples include, but are not limited to, choline ester ^{derivatives and the like, N-alkylmorpholine esters and the like. Other derivatives of the} compounds described herein have activity in both their acid and acid derivative forms, but in the acid sensitive form often offer advantages of solubility, tissue compatibility, or delayed release in the mammalian organism (see, Bundgaard, H., Design of Prodrugs, pp. 7-9, 21-24, Elsevier, Amsterdam 1985). Prodrugs include acid derivatives well known to practitioners of the art, such as, for example, esters prepared by reaction of the parent acid with a suitable alcohol, or amides prepared by reaction of the parent acid compound with a substituted or unsubstituted amine, or acid anhydrides, or mixed anhydrides. Simple aliphatic or aromatic esters, amides, and anhydrides derived from acidic groups pendant on the compounds described herein are particular prodrugs. In some cases, it is desirable to prepare double ester type prodrugs such as (acyloxy)alkyl esters or ((alkoxycarbonyl)oxy)alkylesters. C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, aryl, C7-C12 substituted aryl, and C7-C12 arylalkyl esters of the compounds described herein may be preferred. The terms “composition” and “formulation” are used interchangeably. Protease Inhibitors According to some embodiments, a composition (e.g., a pharmaceutical composition) comprises a protease inhibitor. In some embodiments, the protease is a serine protease, a cysteine protease, or a metalloprotease. In some embodiments, the protease is a serine protease. In certain instances, the serine protease is an S09 type protease (e.g., an S09.13 protease) under the MEROPS classification system. In some embodiments, the protease is configured to cleave GLP-1 and/or GLP-2. In certain embodiments, the protease is configured to preferentially cleave GLP-2 (e.g., the protease has a higher binding affinity for GLP-2 than for GLP-1). In some instances, the protease is DPP-4. In some embodiments, the protease inhibited by the protease inhibitor is an endogenous protease (e.g., DPP-4) expressed by a subject. In some embodiments, the protease inhibited by the protease inhibitor is a microbial protease expressed by a microbial organism (e.g., a bacterium) in the gut microbiome of a subject. In some embodiments, the protease is protease expressed by a bacterium (“a bacterial protease”), such as a protease expressed by bacteria in the gut microbiome of a subject. As used herein, the term “gut microbiome”, sometimes referred to as “gut flora”, “gut microbiota”, or “gut bacteria” refers to microbial organisms (e.g., bacteria, archaea, fungi) that live in the GI tracts of subjects. Studies have shown that bacterial proteases, such as bacterial DPP-4, are not effectively targeted by known inhibitors of the corresponding proteases expressed by human cells (e.g., human DPP-4), such as sitagliptin (Wang, K., et al. (2023). Science, 381(6657), eadd5787.). As described herein and demonstrated in the section entitled “Examples”, inhibition of certain proteases expressed by a bacterium in the gut microbiome may provide advantages for treatment of human disease. In some embodiments, the microbial organism is a bacterium. In some embodiments, the bacterium is a species of Bacteroides bacteria. Non-limiting examples of suitable species of Bacteroides bacteria include B. vulgatus, B. dorei, B. fragilis, B. massiliensis, B. ovatus, B. thetaiotaomicron (also known as B. theta), B. uniformis, B. stercoris, B. cellulosilyticus, B. xylanisolvens, and B. caccae. In some cases, the bacterium is B. vulgatus, B. thetaiotaomicron, and/or B. dorei. In certain instances, the bacterium is B. vulgatus. In some instances, the genera of the bacteria may be from the genera Phocaeicola, which was reclassified from the genera Bacteroides. Non-limiting examples of suitable species of the Phocaeicola genera include P. vulgatus and P. dorei. In some instances, the protease comprises a DPP-4 expressed by B. vulgatus, B. thetaiotaomicron, and/or B. dorei. In some embodiments, a protease inhibitor described herein (e.g., a compound provided herein) is a potent inhibitor of a bacterial protease. In some embodiments, the bacterial protease is a bacterial serine protease, a bacterial cysteine protease, or a bacterial metalloprotease. In certain instances, the bacterial protease is an S09 type protease under the MEROPS classification system. In some embodiments, the bacterial protease is configured to cleave GLP- 1, GLP-2, and/or GIP. In certain embodiments, the bacterial protease is configured to preferentially cleave GLP-2. In some instances, the bacterial protease is DPP-4. In some embodiments, the protease inhibitor inhibits bacterial DPP-4 expressed by a bacterium in the gut microbiome of a subject (e.g., a bacterium of a species of Bacteroides). In some embodiments, the protease inhibitor inhibits bacterial DPP-4 expressed by a bacterium of a species of Bacteroides (e.g., B. vulgatus, B. thetaiotaomicron, B. dorei). In some embodiments, the protease inhibitor reduces activity of the bacterial protease. In some embodiments, the protease inhibitor reduces activity of the bacterial protease by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% compared to its activity in the absence of the protease inhibitor. In some embodiments, a protease inhibitor described herein (e.g., a compound provided herein) is a potent inhibitor of a human protease. In some embodiments, the human protease is a human serine protease, a human cysteine protease, or a human metalloprotease. In some embodiments, the human protease is configured to cleave GLP-1, GLP-2, and/or GIP. In some instances, the human protease is DPP-4. In some embodiments, the protease inhibitor inhibits ^{human DPP-4 expressed by human cells in the gut. In some embodiments, the protease inhibitor} reduces activity of the human protease. In some embodiments, the protease inhibitor reduces activity of the human protease by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% compared to its activity in the absence of the protease inhibitor. In some embodiments, a protease inhibitor described herein (e.g., a compound provided herein) is a potent inhibitor of a microbial (e.g., bacterial) protease and a human protease. In some embodiments, the microbial (e.g., bacterial) protease and/or the human protease are serine proteases, cysteine proteases, and/or metalloproteases. In some embodiments, the microbial (e.g., bacterial) protease and/or the human protease are configured to cleave GLP-1, GLP-2, and/or GIP. In some embodiments, the microbial (bacterial) protease and the human protease are analogous (e.g., homologous) proteases. In some embodiments, the microbial (e.g., bacterial) protease and/or the human protease are DPP-4 (e.g., microbial DPP-4 and/or human DPP-4). In some embodiments, the protease inhibitor inhibits the human protease by a greater percentage than it inhibits the microbial (e.g., bacterial) protease. In some embodiments, the protease inhibitor preferentially inhibits the microbial (e.g., bacterial) protease by a greater percentage than it inhibits the human protease. In some embodiments, the protease inhibitor inhibits the microbial (e.g., bacterial) protease and the human protease at similar percentages. In some embodiments, a protease inhibitor described herein (e.g., a compound provided herein) is a potent inhibitor of bacterial DPP-4 (e.g., DPP-4 of a species of Bacteroides) and human DPP-4. In some embodiments, the protease inhibitor inhibits the bacterial DPP-4 (e.g., DPP-4 of a species of Bacteroides) by a greater percentage than it inhibits the human DPP-4. In some embodiments, the protease inhibitor preferentially inhibits the human DPP-4 by a greater percentage than it inhibits the bacterial DPP-4 (e.g., DPP-4 of a species of Bacteroides). In some embodiments, the protease inhibitor inhibits the bacterial DPP-4 and the human DPP-4 at similar percentages. In some embodiments, the protease inhibitor comprises a gliptin or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. In some embodiments, the protease inhibitor comprises sitagliptin, saxagliptin, teneligliptin, omarigliptin, vildagliptin, or a combination thereof. In some embodiments, the gliptin is sitagliptin or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or ^{prodrug thereof. In some embodiments, the gliptin is saxagliptin or a pharmaceutically} acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. In some embodiments, a protease inhibitor comprises teneligliptin or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. In some embodiments, the gliptin is omarigliptin or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. In some embodiments, the gliptin is vildagliptin or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. In some embodiments, the protease inhibitor is not sitagliptin, saxagliptin, teneligliptin, omarigliptin, or vildagliptin. Structures corresponding to certain known gliptins are provided in FIG. 2. In certain embodiments, a protease inhibitor comprises a compound of Formula (I), a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. These compounds are provided below. Formula (I) In one aspect, provided is a compound of Formula (I):

or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein: R^b is optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted acyl, optionally wherein one or more backbone carbon atoms in the optionally substituted alkyl are independently replaced with –O– or –S-; each instance of R¹¹ is independently hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted carbocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, or a nitrogen protecting group, optionally wherein two instances of R¹¹ are joined together with the nitrogen from which they are attached to form an optionally substituted heterocycle; R^c and R^d are each independently hydrogen, optionally substituted alkyl, halo, -OR^x, or optionally wherein R^c and R^d are joined together to form an optionally substituted C_1-6 carbocycle; R^x is hydrogen, optionally substituted alkyl, or an oxygen protecting group; R¹² is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkenyl, optionally substituted heteroalkynyl, optionally substituted acyl, or azido; and n is 0, 1, or 2; provided that the compound is not of the formula:

. In some embodiments, the pharmaceutically acceptable salt thereof is a formate salt. In some embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, is of the following formulae:

In some embodiments, the compound is of the formula

. some embodiments, the compound is of formula (I-a-I). In some embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, is of Formula (I-a-I):

wherein R¹² is optionally substituted C1-6 alkynyl, optionally substituted C1-6 heteroalkynyl, optionally substituted acyl, or azido. In certain embodiments, R¹² is optionally substituted C1-6 alkyl, optionally substituted C1- 6 alkenyl, optionally substituted C1-6 alkynyl, optionally substituted C1-6 heteroalkyl, optionally substituted C_1-6 heteroalkenyl, optionally substituted C_1-6 heteroalkynyl, or optionally substituted acyl. In some embodiments, R¹² is substituted C1-6 alkyl. In some embodiments, R¹² is substituted C1-3 alkyl. In some embodiments, R¹² is substituted C3-6 alkyl. In some embodiments, R¹² is optionally substituted C_1-6 alkenyl. In some embodiments, R¹² is optionally substituted C_1- ₆ alkynyl. In some embodiments, R¹² is optionally substituted C_1-6 heteroalkyl. In some embodiments, R¹² is optionally substituted C1-6 heteroalkenyl. In some embodiments, R¹² is optionally substituted C1-6 heteroalkynyl. In some embodiments, R¹² is optionally substituted acyl. In certain embodiments, R¹² is optionally substituted C1-6 heteroalkyne or optionally substituted acyl. In certain embodiments, R¹² is of the formula: or , wherein R⁴ is hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted aryl, or optionally substituted heteroaryl. In some embodiments, R⁴ is hydrogen. In some embodiments, R⁴ is optionally substituted alkyl. In some embodiments, R⁴ is optionally substituted heteroalkyl. In some embodiments, R⁴ is optionally substituted aryl. In some embodiments, R⁴ is optionally substituted heteroaryl. In certain embodiments, R⁴ is hydrogen, optionally substituted C1-6 alkyl, or optionally substituted C1-6 heteroalkyl, optionally wherein the optionally substituted C1-6 heteroalkyl is substituted with at least one halogen. In certain embodiments, R⁴ is-H, -CH₃, -CH₂F, -CHF₂, - CF_3, or -CH₂Cl. In some embodiments, R⁴ is methyl, ethyl, propyl, phenyl, butyl, or tert-butyl. In some embodiments, R⁴ is per-halo alkyl. In some embodiments, R⁴ is perfluoroalkyl. In some embodiments, R¹² is of the formula

. In certain embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, is of Formula (I-a-II):

In some embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, is of Formula (I-a-III),

In certain embodiments, R^c and R^d are the same. In certain embodiments, R^c and R^d are the different. In some embodiments, R^c is hydrogen, optionally substituted alkyl, halo, -OR^x. In some embodiments, R^c is hydrogen. In some embodiments, R^c is optionally substituted C1-12 alkyl. In some embodiments, R^c is optionally substituted C1-3 alkyl. In some embodiments, R^c is optionally substituted C_4-8 alkyl. In some embodiments, R^c is optionally substituted C_9-12 alkyl. In some embodiments, R^c is substituted C1-12 alkyl. In some embodiments, R^c is halo (e.g., F, Cl, I, Br). In some embodiments, R^c is -OR^x, wherein R^x is optionally substituted alkyl, hydrogen, or an oxygen protecting group. In some embodiments, R^c is -OH. In some embodiments, R^c is - OMe. In some embodiments, R^d is hydrogen, optionally substituted alkyl, halo, -OR^x. In some embodiments, R^d is hydrogen. In some embodiments, R^d is optionally substituted C_1-12 alkyl. In some embodiments, R^d is optionally substituted C1-3 alkyl. In some embodiments, R^d is optionally substituted C4-8 alkyl. In some embodiments, R^d is optionally substituted C9-12 alkyl. In some embodiments, R^d is substituted C_1-12 alkyl. In some embodiments, R^d is halo (e.g., F, Cl, I, Br). In some embodiments, R^d is -OR^x, wherein R^x is optionally substituted alkyl, hydrogen, or an oxygen protecting group. In some embodiments, R^d is -OH. In some embodiments, R^d is - OMe. In some embodiments, at least one of R^c and R^d is perhaloalkyl. In some embodiments, at least one of R^c and R^d is perfluoroalkyl. In some embodiments, at least one of R^c and R^d is -CF₃. In certain embodiments, at least one of R^c and R^d is hydrogen, optionally substituted C1-6 alkyl, halo, or -OH. In certain embodiments, at least one of R^c and R^d is hydrogen. In certain embodiments, at least one of R^c and R^d is hydrogen and the other is optionally substituted C1-6 alkyl, halo, or -OH. In some embodiments, R^c is hydrogen and R^d is optionally substituted alkyl, halo, -OR^x. In some embodiments, R^d is hydrogen and R^c is optionally substituted alkyl, halo, - OR^x. In certain embodiments, R^c and R^d are joined together to form an optionally substituted C1- 6 carbocycle. In certain embodiments, R^c and R^d are joined together to form an optionally substituted cyclopropyl. In some embodiments, R^d is fluoro. In certain embodiments, R^d is -OH. In some embodiments, each of R^c and R^d is hydrogen and n is 0 or 2. In some embodiments, n is 0. In some embodiments, n is 0 or 1. In some embodiments, n is 1 or 2. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or _{prodrug thereof, is of Formula}

In some embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or _{prodrug thereof, is of Formula ( w d}

_{herein R is optionally} substituted C_1-6 alkyl, halo, or -OH. In some embodiments, the compound is of the formula (I-a- V) wherein R^d is hydroxyl. In some embodiments, the compound is of the formula (I-a-V) wherein R^d is fluoro. In some embodiments, the compound is of the formula (I-a-V) wherein R^d is chloro. In some embodiments, the compound is of the formula (I-a-V) wherein R^d is bromo. In some embodiments, the compound is of the formula (I-a-V) wherein R^d is iodo. In some embodiments, the compound is of the formula (I-a-V) wherein R^d is C_1-6 alkyl. In some embodiments, the compound is of the formula (I-a-V) wherein R^d is perhaloalkyl. In some embodiments, the compound is of the formula (I-a-V) wherein R^d is perfluoroalkyl. In certain embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or _{prodrug thereof, is of Formula (}

_{wherein Rd is halo or -OH. In} some embodiments, the compound is of the formula (I-a-VI) wherein R^d is hydroxyl. In some embodiments, the compound is of the formula (I-a-VI) wherein R^d is fluoro. In some embodiments, the compound is of the formula (I-a-VI) wherein R^d is chloro. In some embodiments, the compound is of the formula (I-a-VI) wherein R^d is bromo. In some embodiments, the compound is of the formula (I-a-VI) wherein R^d is iodo. In some embodiments, R^b is optionally substituted C1-12 carbocyclyl, optionally substituted C1-12 heterocyclyl, optionally substituted C1-6 alkyl, optionally substituted C1-6 heteroalkyl, optionally substituted C_6-14 aryl, optionally substituted C_5-14 heteroaryl, or optionally substituted C1-8 acyl. In some embodiments, R^b is unsubstituted adamantyl, optionally substituted C1-6 alkyl, optionally substituted C1-12 heterocyclyl, optionally substituted C1-6 heteroalkyl, optionally substituted C_6-14 aryl, optionally substituted C_5-8 heteroaryl, or optionally substituted C_1-8 acyl. In some embodiments, R^b is optionally substituted C1-12 carbocyclyl. In some embodiments, R^b is optionally substituted C_1-3 carbocyclyl. In some embodiments, R^b is optionally substituted C_3-6 carbocyclyl. In some embodiments, R^b is optionally substituted C_6-9 carbocyclyl. In some embodiments, R^b is optionally substituted C9-12 carbocyclyl. In some embodiments, R^b is unsubstituted adamantyl. In some embodiments, R^b is substituted adamantyl. In some embodiments, R^b is hydroxy substituted adamantyl. In some embodiments, R^b is hydrogen. In some embodiments, R^b is optionally substituted C1-12 heterocyclyl. In some embodiments, R^b is optionally substituted C_1-3 heterocyclyl. In some embodiments, R^b is optionally substituted C_3-6 heterocyclyl. In some embodiments, R^b is optionally substituted C_6-9 heterocyclyl. In some embodiments, R^b is optionally substituted C9-12 heterocyclyl. In some embodiments, R^b is optionally substituted C1-6 alkyl. In some embodiments, R^b is optionally substituted C_1-3 alkyl. In some embodiments, R^b is optionally substituted C_3-6 alkyl. In some embodiments, R^b is optionally substituted C1-6 aryl. In some embodiments, R^b is optionally substituted phenyl. In some embodiments, R^b is optionally substituted C1-6 heteroalkyl. In some embodiments, R^b is optionally substituted C_1-6 heteroalkyl. In some embodiments, R^b is optionally substituted C1-3 heteroalkyl. In some embodiments R^b is optionally substituted C3-6 heteroalkyl. In certain embodiments, at least one backbone carbon atom in the optionally substituted C_1-6 heteroalkyl is independently replaced with oxygen, nitrogen, sulfur, or a carbonyl. In certain embodiments, R^b is optionally substituted C1-6 alkyl, wherein the optionally substituted C_1-6 alkyl is substituted with at least one halogen. In certain embodiments, R^b is optionally substituted C_1-6 alkyl, wherein the optionally substituted C_1-6 alkyl is substituted with one halogen. In certain embodiments, R^b is optionally substituted C1-6 alkyl, wherein the optionally substituted C1-6 alkyl is substituted with at least two halogens. In certain embodiments, R^b is optionally substituted C_1-6 alkyl, wherein the optionally substituted C_1-6 alkyl is substituted with at least three halogens. In certain embodiments, R^b is optionally substituted C1-6 alkyl, wherein the optionally substituted C1-6 alkyl is substituted with fluorine, chlorine, bromine, or iodine. In certain embodiments, the optionally substituted C_1-6 alkyl is substituted with chlorine. In certain embodiments, the optionally substituted C1-6 alkyl is substituted with bromine. In certain embodiments, the optionally substituted C1-6 alkyl is substituted with iodine. In certain embodiments, the optionally substituted C_1-6 alkyl is substituted with chlorine, bromine, or iodine. In certain embodiments, R^b is optionally substituted C1-6 alkyl, wherein the optionally substituted C1-6 alkyl is substituted with at least one fluorine. In some embodiments, the optionally substituted C_1-6 alkyl is substituted with at least two fluorines. In some embodiments, the optionally substituted C1-6 alkyl is substituted with at least three fluorines. In certain embodiments, R^b is optionally substituted C1-6 alkyl, wherein the optionally substituted C_1-6 alkyl is perfluorinated. In certain embodiments, R^b is optionally substituted C1-6 heteroalkyl, optionally wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –O–, –NR⁵–, =N–, –N=, –S–, –S(=O)–, –S(=O)₂–, –C(=O)–, wherein R⁵ is hydrogen or optionally substituted alkyl (e.g., methyl, ethyl). In certain embodiments, R^b is optionally substituted C1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C_1-6 alkyl are independently replaced with –O–, –NR⁵–, =N–, –N=, –S–, – S(=O)–, –S(=O)₂–, or –C(=O)–. In certain embodiments, R^b is optionally substituted C_1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –O–. In certain embodiments, R^b is optionally substituted C_1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –NR⁵–. In certain embodiments, R^b is optionally substituted C_1- 6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with =N– or –N=. In certain embodiments, R^b is optionally substituted C_1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with–S–, –S(=O)–, –S(=O)2–, –C(=O)–. In certain embodiments, R^b is optionally substituted C1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C_1-6 alkyl are independently replaced with – C(=O)–. In certain embodiments, R^b is optionally substituted C_1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –O– and/or –C(=O)–. In certain embodiments, R^b is optionally substituted C_5-14 heteroaryl. In certain embodiments, R^b is optionally substituted C5-8 heteroaryl. In certain embodiments, R^b is optionally substituted C8-14 heteroaryl. In certain embodiments, at least one backbone carbon atoms in the optionally substituted C_8-14 heteroaryl are independently replaced with oxygen or nitrogen. In some embodiments, R^b is optionally substituted C1-8 acyl. In some embodiments, R^b is optionally substituted C1-3 acyl. In some embodiments, R^b is optionally substituted C4-8 acyl. In some embodiments, R^b is optionally substituted C_1-6 alkyl, wherein the optionally substituted C1-6 alkyl is substituted with at least one halogen. In some embodiments, R^b is optionally substituted C1-6 alkyl, wherein the optionally substituted C1-6 alkyl is substituted with at least two halogens. In some embodiments, R^b is optionally substituted C_1-6 alkyl, wherein the optionally substituted C1-6 alkyl is substituted with at least three halogens. In some embodiments, wherein R^b is optionally substituted C1-6 alkyl, wherein the optionally substituted C_1-6 alkyl is substituted with fluorine, chlorine, bromine, or iodine. In some embodiments, wherein R^b is optionally substituted C1-6 alkyl, wherein the optionally substituted C1-6 alkyl is substituted chlorine, bromine, or iodine. In some embodiments, wherein R^b is optionally substituted C_1-6 alkyl, wherein the optionally substituted C_1-6 alkyl is substituted bromine, or iodine. In some embodiments, wherein R^b is optionally substituted C_1-6 alkyl, wherein the optionally substituted C1-6 alkyl is substituted iodine. In some embodiments, wherein R^b is ^{optionally substituted C} _1-6 ^{alkyl, wherein the optionally substituted C} _1-6 ^{alkyl is substituted} bromine. In some embodiments, wherein R^b is optionally substituted C_1-6 alkyl, wherein the optionally substituted C1-6 alkyl is substituted chlorine. In some embodiments, wherein R^b is optionally substituted C_1-6 alkyl, wherein the optionally substituted C_1-6 alkyl is substituted with at least one fluorine. In some embodiments, wherein R^b is optionally substituted C1-6 alkyl, wherein the optionally substituted C_1-6 alkyl is substituted with at least two fluorines. In some embodiments, wherein R^b is optionally substituted C1-6 alkyl, wherein the optionally substituted C1-6 alkyl is substituted with at least three fluorines. In some embodiments, wherein R^b is optionally substituted C_1-6 alkyl, wherein the optionally substituted C_1-6 alkyl is pefluoroalkyl. In certain embodiments, wherein R^b is optionally substituted C1-6 heteroalkyl, optionally wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –O–, –NR⁵–, =N–, –N=, –S–, –S(=O)–, –S(=O)₂–, –C(=O)–, wherein R⁵ is hydrogen or methyl. In certain embodiments, wherein R^b is optionally substituted C1-6 heteroalkyl, one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –O–, –NR⁵–, =N–, –N=, –S–, –S(=O)–, –S(=O)2–, or –C(=O). In certain embodiments, wherein R^b is optionally substituted C_1-6 heteroalkyl, one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with - O-. In certain embodiments, wherein R^b is optionally substituted C1-6 heteroalkyl, one or more backbone carbon atoms in the optionally substituted C_1-6 alkyl are independently replaced with - --NR⁵–. In certain embodiments, wherein R^b is optionally substituted C1-6 heteroalkyl, one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with =N– or–N=. In certain embodiments, wherein R^b is optionally substituted C_1-6 heteroalkyl, one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with–S–, –S(=O)–, –S(=O)2–, or –C(=O)–. In some embodiments, R^b is optionally substituted alkyl or optionally substituted carbocyclyl. In certain embodiments, R^b is optionally substituted C3-12 carbocyclyl or optionally substituted C_1-6 alkyl. In some embodiments, R^b is optionally substituted C_3-12 carbocyclyl. In certain embodiments, R^b is of the formula:

, w e e , Y is H, CH₃, CH₂F, CHF₂, CF₃, Cl, Br, I, F, or OH; Z is optionally substituted alkyl, optionally substituted amine, optionally substituted carbocyclyl, or optionally substituted aryl; W is hydrogen, optionally substituted alkyl, or optionally substituted heteroalkyl; Y’ is hydrogen, optionally substituted alkyl, optionally substituted aryl, halo, or hydroxyl; and m is 0, 1, or 2. In some embodiments, at least one of R^b is of the formula

. In some

embodiments, at least one of R^b is of the formula . In some embodiments, at least one of R^b is of the formula . In some embodiments, at least one of R^b is of the formula

. some embodiments, at least one of R^b is of the formula

. In some embodiments, at least one of R^b is of the formula

. In some embodiments, m is 0,1, 2, 3, or 4. In some embodiments, m is 1, 2, 3, or 4. In some embodiments, m is 2, 3, or 4. In some embodiments m is 1 or 2. In some embodiments, m is 3 or 4. In some embodiments, m is 0. In certain embodiments, m is 1. In certain embodiments, m is 2. In certain embodiments, m is 3. In certain embodiments, m is 4. In some embodiments, m is more than 4. In some embodiments, R^b is of the formula:

ments, R^b is of the formula

. In some embodiments, R^b is of

the formula . In some embodiments, R^b is of the formula

. In some embodiments, R^b is of the formula

. In some embodiments, R^b is of the formula

.In some embodiments, R^b is of the formula

. In certain embodiments, R^b is of the formula:

, , ,

the formula

. In some embodiments, Rb is of the formula

. In some embodiments, Rb is of the formula . In some embodiments, Rb is of the formula

. In some embodiments, Rb is of the formula

some embodiments, Rb is of the formula

. In some embodiments, Rb is of the formula

. In some _{embodiments, Rb is of the formula}

_{some embodiments, Rb is of the formula}

_{some embodiments, Rb is of the formula}

_{. In some embodiments, Rb} is of the formula

. some embodiments, R^b is of the formula

. In some embodiments, R^b is of the formula

. embodiments, R^b is of the formula

. In some embodiments, R^b is of the formula

. In certain embodiments R^b is of the formula:

is hydrogen, optionally substituted C_1-6 alkyl, halo, or -OR^x; and A is -S- or absent. In certain bodiments R^b

em is . In certain embodiments

. some embodiments, Y is methyl, ethyl, fluoro, chloro, hydroxyl, or hydrogen. In certain embodiments R^b is

methyl. In certain embodiments

ethyl. In certain

embodiments R^b is and Y is fluoro. In certain embodiments R^b is and Y is chloro. In certain embodiments

hydroxyl. In certain embodiments

r hydrogen. In certain embodiments

halo. In certain embodiments R^b is

, A is -S-, and Y is methyl. In certain mbodiments R^b

e is , A is -S-, and Y is ethyl. In certain embodiments R^b is , A is -S-, and Y is fluoro. In certain embodiments R^b is

, A is -S-, and Y is chloro. In certain embodiments R^b

is

, A is -S-, and Y is hydroxyl. In certain embodiments R^b is

, A is -S-, and Y is or hydrogen. In certain embodiments R^b is

, A is -S-, and Y is halo.

In certain embodiments R^b is , A is absent, and Y is methyl. In certain mbodiments R^b

e is , A is absent, and Y is ethyl. In certain embodiments R^b is ,

A is absent, and Y is fluoro. In certain embodiments R^b is , A is absent, and Y is

chloro. In certain embodiments R^b is , A is absent, and Y is hydroxyl. In certain embodiments R^b is

, A is absent, and Y is or hydrogen. In certain embodiments R^b is

absent, and Y is halo. In certain embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, is of Formula

wherein Y is hydrogen, optionally substituted C1-6 alkyl, halo, or -OR^x. In certain embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, is of Formula (I-b-I):

wherein Y is hydrogen. In certain embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, is of Formula (I-b-I):

wherein Y is optionally substituted C_1-6 alkyl (e.g., methyl, ethyl, tert-butyl, propyl, isopropyl) . In certain embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, is of Formula

wherein Y is halo (e.g., I, Br, F, Cl). In certain embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, is of Formula (I-b-I):

wherein Y is or -OR^x, wherein R^x is hydrogen, alkyl, or oxygen protecting group. In some embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or _{prodrug thereof, is of Formula (}

In certain embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, is of Formula (I-b-III):

In some embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or _{prodrug thereof, is of Formula}

In certain embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or _{prodrug thereof, is of Formula (}

In certain embodiments, at least one of R¹¹ is hydrogen, optionally substituted C1-6 alkyl, C1-6 optionally substituted heteroalkyl, C1-12 optionally substituted carbocyclyl, nitrogen protecting group or C_1-6 optionally substituted aryl. In some embodiments, at least one of R¹¹ is optionally substituted C1-6 alkyl. In some embodiments, at least one of R¹¹ is optionally substituted C1-3 alkyl. In some embodiments, at least one of R¹¹ is optionally substituted C3-6 alkyl. In some embodiments, at least one of R¹¹ is optionally substituted C_1-6 heteroalkyl. In some embodiments, at least one of R¹¹ is optionally substituted C3-6 heteroalkyl. In some embodiments, of R¹¹ is optionally substituted C3-6 heteroalkyl. In some embodiments, at least one of R¹¹ is C_1-12 optionally substituted carbocyclyl. In some embodiments, at least one of R¹¹ is C1-3 optionally substituted carbocyclyl. In some embodiments, at least one of R¹¹ is C3-6 optionally substituted carbocyclyl. In some embodiments, at least one of R¹¹ is C6-9 optionally substituted carbocyclyl. In some embodiments, at least one of R¹¹ is C_9-12 optionally substituted carbocyclyl. In some embodiments, at least one of R¹¹ is C_1-6 optionally substituted aryl. In certain embodiments, at least one of R¹¹ is phenyl. In certain embodiments, at least one of R¹¹ is phenyl substituted with at least one fluorine. In some embodiments, at least one of R¹¹ is optionally substituted C_1-6 heteroalkyl, optionally wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –O–, –NR⁵–, =N–, –N=, –S–, –S(=O)–, –S(=O)2–, –C(=O)–, wherein R⁵ is hydrogen or methyl. In certain embodiments, at least one of R¹¹ is optionally substituted C1-6 heteroalkyl, optionally wherein one or more backbone carbon atoms in the optionally substituted C1-6 heteroalkyl are independently replaced with –O–, –NR⁵–, =N–, –N=, –S–, –S(=O)–, –S(=O)₂–, –C(=O)–, wherein R⁵ is hydrogen or methyl. In certain embodiments, at least one of R¹¹ is optionally substituted C1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –O–, – NR⁵–, =N–, –N=, –S–, –S(=O)–, –S(=O)₂–, or –C(=O)–. In certain embodiments, at least one of R¹¹ is optionally substituted C1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –O–. In certain embodiments, at least one of R¹¹ is optionally substituted C_1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –NR⁵–. In certain embodiments, at least one of R¹¹ is optionally substituted C1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C_1-6 alkyl are independently replaced with =N– or –N=. In certain embodiments, at least one of R¹¹ is optionally substituted C_1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl ^{are independently replaced with–S–, –S(=O)–, –S(=O)} ₂ ^{–, –C(=O)–. In certain embodiments, at} least one of R¹¹ is optionally substituted C_1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –C(=O)–. In certain embodiments, at least one of R¹¹ is optionally substituted C_1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –O– and/or –C(=O)–. In certain embodiments, at least one of R¹¹ is hydrogen. In certain embodiments, at least one of R¹¹ is optionally substituted C1-6 alkyl. In certain embodiments, at least one of R¹¹ is methyl. In certain embodiments, at least one of R¹¹ is ethyl. In certain embodiments, at least one of R¹¹ is propyl. In certain embodiments, at least one of R¹¹ is isopropyl. In certain embodiments, at least one of R¹¹ is butyl. In certain embodiments, at least one of R¹¹ is tert-butyl. In some embodiments, each instance of R¹¹ is hydrogen or methyl. In some embodiments, at least one instance of R¹¹ is hydrogen, optionally substituted C_1-6 alkyl, or optionally substituted acyl. In certain embodiments at least one instance of R¹¹ is hydrogen, methyl, or optionally substituted acyl. In certain embodiments, the optionally substituted acyl is a substituted ester. In some embodiments, the substituted ester is of the formula

, wherein each R^N is independently hydrogen, optionally substituted C1-6 alkyl, or nitrogen protecting group. In certain embodiments, the compound is a compound shown in Table 1.

or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. In certain embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, is:

certain embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, is

. In certain embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically _{labeled compound, or prodrug thereof,}

_{certain embodiments, the} compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, is

. In some embodiments, a compound of Formula (I) (e.g., a compound shown in Table 1, a compound of any one of Compound No. 26-57) is an inhibitor of a protease. In some embodiments, a compound of Formula (I) is an inhibitor of a human protease. In some embodiments, a compound of Formula (I) is an inhibitor of a bacterial protease. In some embodiments, a compound of Formula (I) is an inhibitor of a protease expressed by a bacterium associated with glucose metabolism and/or regulation. In some embodiments, a compound of Formula (I) is an inhibitor of a protease expressed by a bacterium of a species of Bacteroides (e.g., B. vulgatus, B. dorei, B. fragilis, B. massiliensis, B. ovatus, B. thetaiotaomicron (also known as B. theta), B. uniformis, B. stercoris, B. cellulosilyticus, B. xylanisolvens, B. caccae) or Phocaeicola (e.g., P. vulgatus and P. dorei). In some embodiments, a compound of Formula (I) is an inhibitor of a serine protease, a cysteine protease, or a metalloprotease. In certain embodiments, a compound of Formula (I) is an inhibitor of a serine protease. In certain instances, a compound of Formula (I) is an inhibitor of a S09 type protease (e.g., an S09.13 protease) under the MEROPS classification system. In some embodiments, a compound of Formula (I) is an inhibitor of a protease configured to cleave GLP-1, GLP-2 and/or GIP. In some embodiments, a compound of Formula (I) is an inhibitor of DPP-4. In some embodiments, a compound of Formula (I) is an inhibitor of human DPP-4. In some embodiments, a compound of Formula (I) is an inhibitor of a bacterial DPP-4. In some embodiments, a compound of Formula (I) is an inhibitor of a DPP-4 expressed by B. vulgatus, B. thetaiotaomicron, and/or B. dorei. Formula (II) In one aspect, provided herein is a compound of Formula (II):

. In some embodiments, the pharmaceutically acceptable salt thereof is a formate salt. In some embodiments, provided herein is a compound of Formula (II-a):

or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. In certain embodiments, provided herein is a compound of Formula (II-b):

or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. In some embodiments, n' is 0. In some embodiments, n' is 0 or 1. In some embodiments, n' is 1 or 2. In some embodiments, n' is 1. In some embodiments, n' is 2. In some embodiments, each instance of R^a is independently hydrogen, optionally substituted C1-12 carbocyclyl, optionally substituted C1-6 alkyl, optionally substituted C1-6 heteroalkyl, optionally substituted C6-14 aryl, optionally substituted C5-14 heteroaryl, optionally substituted C_1-8 acyl, or optionally substituted alkyl wherein the alkyl chains are joined, including the nitrogen atom to which they are attached, to form an optionally substituted heterocyclyl. In some embodiments, each instance of R^a is the same. In some embodiments, each instance of R^a is different. In certain embodiments, at least one instance of R^a is hydrogen, and the second instance of R^a is optionally substituted C1-12 carbocyclyl, optionally substituted C1-6 alkyl, optionally substituted C1-6 heteroalkyl, optionally substituted C6-14 aryl, optionally substituted C6-14 heteroaryl, optionally substituted C_1-8 acyl, or optionally substituted alkyl wherein the alkyl chains are joined, including the nitrogen atom to which they are attached, to form an optionally substituted heterocyclyl. In some embodiments, one instance of R^a is hydrogen, and the second instance of R^a is unsubstituted adamantyl, optionally substituted C1-6 alkyl, optionally substituted C1-6 heteroalkyl, optionally substituted C6 aryl, optionally substituted C6 heteroaryl, optionally substituted C1-8 acyl, or optionally substituted alkyl wherein the alkyl chains are joined, including the nitrogen atom to which they are attached, to form an optionally substituted heterocyclyl. In some embodiments, at least one of R^a is hydrogen. In some embodiments, at least one of R^a is unsubstituted adamantyl. In some embodiments, at least one of R^a is substituted adamantyl. In some embodiments, at least one of R^a is hydroxy-substituted adamantyl. In some embodiments, at least one of R^a is optionally substituted C1-6 alkyl. In some embodiments, at least one of R^a is optionally substituted C_1-3 alkyl. In some embodiments, at least one of R^a is optionally substituted C_3-6 alkyl. In some embodiments, at least one of R^a is optionally substituted C1-6 heteroalkyl, . In ^{some embodiments, at least one instance of Ra is optionally substituted C} _1-6 ^{heteroalkyl. In some} embodiments, at least one instance of R^a is optionally substituted C_1-3 heteroalkyl. In some embodiments, at least one instance of R^a is optionally substituted C3-6 heteroalkyl. In certain embodiments, at least one backbone carbon atoms in the optionally substituted C_1-6 heteroalkyl are independently replaced with oxygen, nitrogen, sulfur, or a carbonyl. In some embodiments, at least one of R^a is optionally substituted C_6-14 aryl. In some embodiments, at least one instance of R^a is unsubstituted C6 aryl. In certain embodiments, at least one of R^a is optionally substituted C5-14 heteroaryl. In certain embodiments, at least one of R^a is optionally substituted C₅ heteroaryl. In certain embodiments, at least one of R^a is optionally substituted C5-8 heteroaryl. In certain embodiments, at least one backbone carbon atoms in the optionally substituted C5-12 heteroaryl are independently replaced with oxygen or nitrogen. In some embodiments, at least one of R^a is optionally substituted C_1-8 acyl. In some embodiments, at least one of R^a is optionally substituted C1-4 acyl. In some embodiments, each R^a is or optionally substituted alkyl wherein the alkyl chains are joined, including the nitrogen atom to which they are attached, to form an optionally substituted heterocyclyl. In some embodiments, at least one instance of R^a is optionally substituted C1-12 carbocyclyl. In some embodiments, at least one instance of R^a is optionally substituted C1-3 carbocyclyl. In some embodiments, at least one instance of R^a is optionally substituted C_3-6 carbocyclyl. In some embodiments, at least one instance of R^a is optionally substituted C6-9 carbocyclyl. In some embodiments, at least one instance of R^a is optionally substituted C9-12 carbocyclyl. In some embodiments, at least one instance of R^a is optionally substituted C_1-6 alkyl. In some embodiments, the optionally substituted C1-6 alkyl is substituted with at least one halo (e.g., Cl, Br, I, F). In some embodiments, the optionally substituted C1-6 alkyl is substituted with at least one fluorine. In some embodiments, at least one instance of R^a is optionally substituted C1-3 alkyl. In some embodiments, at least one instance of R^a is optionally substituted C3-6 alkyl. In some embodiments, at least one instance of R^a is optionally substituted C_6-14 aryl. In some embodiments, at least one instance of R^a is optionally substituted phenyl. In some embodiments, at least one instance of R^a is optionally substituted C5-14 heteroaryl. In some embodiments, at least one instance of R^a is optionally substituted C_1-8 acyl. In some embodiments, at least one instance of R^a is optionally substituted C_1-3 acyl. In some embodiments, at least one instance of R^a is optionally substituted C4-8 acyl. In some ^{embodiments, at least one instance of Ra is or optionally substituted alkyl wherein the alkyl} chains are joined, including the nitrogen atom to which they are attached, to form an optionally substituted heterocyclyl. In certain embodiments, R^a is optionally substituted C1-6 alkyl, wherein the optionally substituted C_1-6 alkyl is substituted with at least one halogen. In certain embodiments, R^a is optionally substituted C1-6 alkyl, wherein the optionally substituted C1-6 alkyl is substituted with one halogen. In certain embodiments, R^a is optionally substituted C1-6 alkyl, wherein the optionally substituted C_1-6 alkyl is substituted with at least two halogens. In certain embodiments, R^a is optionally substituted C1-6 alkyl, wherein the optionally substituted C1-6 alkyl is substituted with at least three halogens. In certain embodiments, R^a is optionally substituted C_1-6 alkyl, wherein the optionally substituted C_1-6 alkyl is substituted with fluorine, chlorine, bromine, or iodine. In certain embodiments, the optionally substituted C_1-6 alkyl is substituted with chlorine. In certain embodiments, the optionally substituted C1-6 alkyl is substituted with bromine. In certain embodiments, the optionally substituted C1-6 alkyl is substituted with iodine. In certain embodiments, the optionally substituted C_1-6 alkyl is substituted with chlorine, bromine, or iodine. In certain embodiments, R^a is optionally substituted C1-6 alkyl, wherein the optionally substituted C1-6 alkyl is substituted with at least one fluorine. In some embodiments, the optionally substituted C_1-6 alkyl is substituted with at least two fluorines. In some embodiments, the optionally substituted C1-6 alkyl is substituted with at least three fluorines. In certain embodiments, R^a is optionally substituted C1-6 alkyl, wherein the optionally substituted C_1-6 alkyl is perfluorinated. In certain embodiments, R^a is optionally substituted C1-6 heteroalkyl, optionally wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –O–, –NR⁵–, =N–, –N=, –S–, –S(=O)–, –S(=O)₂–, –C(=O)–, wherein R⁵ is hydrogen or optionally substituted alkyl (e.g., methyl, ethyl) . In certain embodiments, R^a is optionally substituted C1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C_1-6 alkyl are independently replaced with –O–, –NR⁵–, =N–, –N=, –S–, – S(=O)–, –S(=O)2–, or –C(=O)–. In certain embodiments, R^a is optionally substituted C1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –O–. In certain embodiments, R^a is optionally substituted C_1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C_1-6 alkyl are independently replaced with –NR⁵–. In certain embodiments, R^a is optionally substituted C1-6 ^{heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C} _1-6 ^alkyl are independently replaced with =N– or –N=. In certain embodiments, R^a is optionally substituted C1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C_1-6 alkyl are independently replaced with–S–, –S(=O)–, –S(=O)₂–, –C(=O)–. In certain embodiments, R^a is optionally substituted C1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C_1-6 alkyl are independently replaced with – C(=O)–. In certain embodiments, R^a is optionally substituted C1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –O– and/or –C(=O)–. In certain embodiments, each R^a is independently of formula:

, Y is H, CH3, CH2F, CHF2, CF3, Cl, Br, I, F, or OH; A is -CH2- or -S-; Z is optionally substituted alkyl, optionally substituted amine, optionally substituted carbocyclyl, or optionally substituted aryl; W is hydrogen, optionally substituted alkyl, or optionally substituted heteroalkyl; and m is 0, 1, or 2. In some embodiments, at least one of R^a is of the formula

. In some

embodiments, at least one of R^a is of the formula

. In some embodiments, at least one of R^a is of the formula

. some embodiments, at least one of R^a is of the formula

. In some embodiments, at least one of R^a is of the formula

. In some embodiments, m is 0,1, 2, 3, or 4. In some embodiments, m is 1, 2, 3, or 4. In some embodiments, m is 2, 3, or 4. In some embodiments m is 1 or 2. In some embodiments, m is 3 or 4. In some embodiments, m is 0. In certain embodiments, m is 1. In certain embodiments, m is 2. In certain embodiments, m is 3. In certain embodiments, m is 4. In some embodiments, m is more than 4. In some embodiments, each R^a is independently hydrogen or of formula:

In some embodiments, at least one instance of R^a is hydrogen. In some embodiments, one R^a is hydrogen, and the other R^a is of the formula

. In some embodiments, one R^a is hydrogen, and the other R^a is of the formula

. some embodiments, one R^a is hydrogen, and the other R^a is of the formula

. In some embodiments, one R^a is hydrogen, and the other R^a is of the formula

. In some embodiments, at least one of R^a is of the formula

. some embodiments, at least one of R^a is of the formula

. In some embodiments, at least one of R^a is of the formula

. In some embodiments, one instance of R^a is hydrogen and the other is of the formula:

embodiments, at least one instance of R^a is hydrogen. In some embodiments, one R^a is hydrogen, and the other R^a is of the formula

. In some embodiments, one R^a is hydrogen, and the other R^a is of the formula

. In some embodiments, one R^a is hydrogen, and the other

a

_{R is of the formula . In some embodiments, one Ra is hydrogen, and the other Ra is of} _{the formula . In some embodiments, one Ra is hydrogen, and the other Ra is of the}

_{formula . In some embodiments, one Ra is hydrogen, and the other Ra is of the formula} In some embodiments, one R^a is hydrogen, and the other R^a is of the formula

. some embodiments, one R^a is hydrogen, and the other R^a is of the formula

. In some embodiments, one R^a is hydrogen, and the other R^a is of the formula . In some embodiments, one R^a is hydrogen, and the other R^a is of the formula . In some embodiments, one R^a is hydrogen, and the other R^a is of the formula

. some embodiments, one R^a is hydrogen, and the other R^a is of the formula

. some embodiments, one R^a is hydrogen, and the other R^a is of the formula e embodiments, one R^a is hydrogen, and the other R^a is of the formula

_{some embodiments, at least one of Ra is of the formula}

_. In some embodiments, at least one of R^a is of the formula

I_{n some embodiments, -N(Ra)2 is of the formula:}

wherein Y’ is hydrogen, optionally substituted alkyl, optionally substituted aryl, halo, or hydroxyl. In some embodiments, -N(R^a)2 is of the formula

. In some _{embodiments, -N(Ra)2 is of the formula:}

_{, wherein p and q are independently 1,} 2, or 3. In some embodiments, N(R^a)2 is of the formula:

_{is of the formula}

. In some embodiments, N(R^a)2 is of the formula

. embodiments, N(R^a)2 is of the formula

. In some embodiments, N(R^a)2 is of the formula

. In some embodiments, R¹ is hydrogen, optionally substituted C_1-6 alkyl, C_1-6 optionally substituted heteroalkyl, C1-12 optionally substituted carbocyclyl, or C1-6 optionally substituted aryl. In certain embodiments, R¹ is phenyl. In certain embodiments, R¹ is substituted phenyl. In certain embodiments, R¹ is phenyl substituted with at least one fluorine. In some embodiments, R¹ is hydrogen. In some embodiments, R¹ is optionally substituted C1-6 alkyl. In some embodiments, R¹ is C_1-6 optionally substituted heteroalkyl. In some embodiments, R¹ is C_1-12 optionally substituted carbocyclyl. In some embodiments, R¹ is C_1-6 optionally substituted aryl. In certain embodiments, R¹ is optionally substituted C1-6 heteroalkyl, optionally wherein one or more backbone carbon atoms in the optionally substituted C1-6 heteroalkyl are independently replaced with –O–, –NR⁵–, =N–, –N=, –S–, –S(=O)–, –S(=O)₂–, –C(=O)–, wherein R⁵ is hydrogen or methyl. In certain embodiments, R¹ is optionally substituted C1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –O–, –NR⁵–, =N–, –N=, –S–, –S(=O)–, –S(=O)₂–, or –C(=O)–. In certain embodiments, R¹ is optionally substituted C1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with – O–. In certain embodiments, R¹ is optionally substituted C1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C_1-6 alkyl are independently replaced with – NR⁵–. In certain embodiments, R¹ is optionally substituted C1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with =N– or –N=. In certain embodiments, R¹ is optionally substituted C_1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with–S–, –S(=O)–, –S(=O)2–, –C(=O)–. In certain embodiments, R¹ is optionally substituted C_1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C_1-6 alkyl are independently replaced with –C(=O)–. In certain embodiments, R¹ is optionally substituted C1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –O– and/or –C(=O)–. In certain embodiments, R¹ is hydrogen. In certain embodiments, R¹ is methyl. In certain embodiments, R¹ is ethyl. In certain embodiments, R¹ is propyl. In certain embodiments, R¹ is isopropyl. In certain embodiments, R¹ is butyl. In certain embodiments, R¹ is tert-butyl. In some embodiments, R² is optionally substituted C_1-6 alkyl, optionally substituted C_1-6 alkenyl, optionally substituted C1-6 alkynyl, optionally substituted C1-6 heteroalkyl, optionally substituted C1-6 heteroalkenyl, optionally substituted C1-6 heteroalkynyl, or optionally substituted acyl. In some embodiments, R² is substituted C_1-6 alkyl. In some embodiments, R² is substituted C1-3 alkyl. In some embodiments, R² is substituted C3-6 alkyl. In some embodiments, R² is optionally substituted C1-6 alkenyl. In some embodiments, R² is optionally substituted C1-6 alkynyl. In some embodiments, R² is optionally substituted C_1-6 heteroalkyl. In some embodiments, R² is optionally substituted C1-6 heteroalkenyl. In some embodiments, R² is optionally substituted C1-6 heteroalkynyl. In some embodiments, R² is optionally substituted acyl. In some embodiments, R² is optionally substituted C1-6 heteroalkyne or optionally substituted acyl. In some embodiments, R² is of the formula:

, wherein R⁴ is hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted aryl, or optionally substituted heteroaryl. In some embodiments, R⁴ is hydrogen. In some embodiments, R⁴ is optionally substituted alkyl. In some embodiments, R⁴ is optionally substituted heteroalkyl. In some embodiments, R⁴ is optionally substituted aryl. In some embodiments, R⁴ is optionally substituted heteroaryl. In certain embodiments, R⁴ is hydrogen, optionally substituted C1-6 alkyl, or optionally substituted C_1-6 heteroalkyl, optionally wherein the optionally substituted C_1-6 heteroalkyl is substituted with at least one halogen. In certain embodiments, R⁴ is-H, -CH3, -CH2F, -CHF2, - CF3, or -CH2Cl. In some embodiments, R⁴ is methyl, ethyl, propyl, phenyl, butyl, or tert-butyl. In some embodiments, R⁴ is per-halo alkyl. In some embodiments, R⁴ is perfluoroalkyl. In some embodiments, R² is of the formula

. In certain embodiments, X is hydrogen, hydroxyl, halogen, or optionally substituted C1-6 heteroalkyl. In some embodiments, X is hydrogen. In some embodiments, X is hydroxyl. In some embodiments, X is optionally substituted C_1-6 heteroalkyl. In some embodiments, X is optionally substituted C6-14 heteroaryl. In some embodiments, X is optionally substituted C1-6 alkyl. In some embodiments, X is fluorine. In some embodiments, X is chlorine. In some embodiments, X is optionally substituted C_1-6 heteroalkyl, optionally wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –O–, –NR⁵–, =N–, –N=, –S–, –S(=O)–, –S(=O)2–, –C(=O)–, wherein R⁵ is hydrogen or methyl. In certain embodiments, X is optionally substituted C_1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –O–, –NR⁵–, =N–, –N=, –S–, –S(=O)–, –S(=O)2–, or –C(=O)–. In certain embodiments, X is optionally substituted C_1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –O–. In certain embodiments, X is optionally substituted C1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C_1-6 alkyl are independently replaced with –NR⁵–. In certain embodiments, X is optionally substituted C_1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with =N– or – N=. In certain embodiments, X is optionally substituted C_1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with– S–, –S(=O)–, –S(=O)2–, –C(=O)–. In certain embodiments, X is optionally substituted C1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C_1-6 alkyl are independently replaced with –C(=O)–. In certain embodiments, X is optionally substituted C1-6 heteroalkyl, wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –O– and/or –C(=O)–. In certain embodiments, provided in the present disclosure is a compound described herein, wherein the compound is a compound shown in Table 2. _{Table 2: Exemplary Compounds of Formula (II)}

or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, _{stereoisomer, isotopically labeled compound, or prodrug thereof. In some embodiments,} provided is a compound described herein or a pharmaceutically acceptable salt or other form thereof. In some embodiments, a compound of Formula (II) (e.g., a compound shown in Table 2, compound of any one of Compound No. 1-24) is an inhibitor of a protease. In some embodiments, a compound of Formula (II) is an inhibitor of a human protease. In some embodiments, a compound of Formula (II) is an inhibitor of a bacterial protease. In some embodiments, a compound of Formula (II) is an inhibitor of a protease expressed by a bacterium associated with glucose metabolism and/or regulation. In some embodiments, a compound of Formula (II) is an inhibitor of a protease expressed by a bacterium of a species of Bacteroides (e.g., B. vulgatus, B. dorei, B. fragilis, B. massiliensis, B. ovatus, B. thetaiotaomicron (also known as B. theta), B. uniformis, B. stercoris, B. cellulosilyticus, B. xylanisolvens, B. caccae) or Phocaeicola (e.g., P. vulgatus and P. dorei). In some embodiments, a compound of Formula (II) is an inhibitor of a serine protease, a cysteine protease, or a metalloprotease. In certain embodiments, a compound of Formula (II) is an inhibitor of a serine protease. In certain instances, a compound of Formula (II) is an inhibitor of a S09 type protease (e.g., an S09.13 protease) under the MEROPS classification system. In some embodiments, a compound of Formula (II) is an inhibitor of a protease configured to cleave GLP-1, GLP-2 and/or GIP. In some embodiments, a compound of Formula (II) is an inhibitor of DPP-4. In some embodiments, a compound of Formula (II) is an inhibitor of human DPP-4. In some embodiments, a compound of Formula (II) is an inhibitor of bacterial DPP-4. In some embodiments, a compound of Formula (II) is an inhibitor of a DPP-4 expressed by B. vulgatus, B. thetaiotaomicron, and/or B. dorei. Prophylactic and/or Therapeutic Uses In some embodiments, provided herein are compositions (e.g., pharmaceutical compositions) and methods useful for, inter alia, preventing (e.g., delaying the onset of) or reducing the likelihood of one or more signs or symptoms of a dysfunction of glucose metabolism and/or regulation in a subject, for example, in a subject having or being at risk of developing a dysfunction of glucose metabolism and/or regulation. In some embodiments, provided herein are compositions (e.g., pharmaceutical compositions) and methods useful for, inter alia, alleviating (e.g., reducing or eliminating, slowing the progression) or treating one or more signs or symptoms of a dysfunction of glucose metabolism and/or regulation in a subject, for example, in a subject having one or more signs or symptoms of a dysfunction of glucose metabolism and/or regulation. In some embodiments, compositions (e.g., pharmaceutical compositions) and methods described herein provide one or more prophylactic effects or therapeutic effects to a subject. A “prophylactic effect” refers to an effect which prevents (e.g., delays the onset of) or reduces the likelihood of the development of one or more signs or symptoms of a disorder (e.g., a disorder related to dysfunction of glucose metabolism and/or regulation) in a subject. A “therapeutic effect” refers to an effect which alleviates (e.g., reduces or eliminates, slows the progression) or treats one or more signs or symptoms of a disorder (e.g., a disorder related to dysfunction of glucose metabolism and/or regulation) in a subject. As used herein, the term “treating” refers to providing a prophylactic and/or therapeutic effect to a subject in need thereof. Dysfunctions of Glucose Metabolism and/or Regulation In some embodiments, a composition described herein is used in a method of treating a subject having one or more signs or symptoms of a dysfunction of glucose metabolism and/or regulation. In some embodiments, a composition (e.g., a prophylactic composition) described herein, is used in a method of preventing (e.g., delaying the onset of) and/or reducing the likelihood of the development of one or more signs or symptoms of a dysfunction of glucose metabolism and/or regulation in a subject. In some embodiments, a composition (e.g., a therapeutic composition) described herein is used in a method of alleviating (e.g., delaying or reducing the progression and/or severity of; arresting) one or more signs or symptoms of a dysfunction of glucose metabolism and/or regulation in a subject. As used herein, “glucose metabolism and regulation” refers to any process in a subject associated with the digestion of availability, utilization, or regulation of glucose. Glucose metabolism and/or regulation in a subject is mediated by many factors, including, but not limited to: genes and gene expression; subject or bacterial enzyme (e.g., protease) function; hormonal signaling (e.g., glucoregulatory hormones, such as GLP-1, GLP-2, and/or GIP); organ or tissue function (e.g., GI tract, liver, kidneys, pancreas, thyroid, brain); and diet and activity of the subject. The term “normal glucose metabolism and/or regulation” refers to the ability of a subject to metabolize and maintain normal glucose homeostasis. The term “normal glucose homeostasis” refers to glucose concentrations in the blood within acceptable ranges while fasting and after eating such that tissues and organs of the subject are able to function healthily. In some embodiments, normal glucose homeostasis in a human subject refers to a glucose concentration in the blood within a range of about 70 to 100mg/dL (e.g., 72 to 99mg/dL) while fasting and/or below 140mg/dL two hours after eating. The skilled artisan will appreciate that these ranges may vary based on an individual subject’s medical history, demographic factors (e.g., age, sex), but generally fall within art-recognized ranges (e.g., as described by Güemes, M., et al. (2016). Archives of disease in childhood, 101(6), 569-574.). Regulation of glucose occurs through a number of signaling cascades, but typically ultimately results in catabolism of glycogen, synthesis of glycogen, or transport of glucose in or out of cells by various proteins or peptide-based molecules. For example, when glucose concentrations in the blood rise above a certain level, GLP-1 and GIP, two glucoregulatory hormones, are secreted by L-cells and K-cells in the GI tract, respectively. Binding of either hormone to its respective receptor triggers the secretion of insulin by beta cells in the pancreas. Insulin then decreases levels of glucose in the blood through several mechanisms, for example, by stimulating release of GLUT-4 from intracellular stores, increasing expression of glycogen synthase, and inactivating kinases or decreasing expression of enzymes involved in gluconeogenesis. As used herein, “dysfunctional glucose metabolism and/or regulation” refers to the inability of a subject to maintain glucose homeostasis. In some embodiments, an inability to maintain glucose homeostasis results in glucose concentrations in the blood outside of a range of about 70 to 100mg/dL (e.g., 72 to 99mg/dL) while fasting and/or above 140mg/dL two hours after eating. In some embodiments, a subject having one or more signs of dysfunctional glucose metabolism and/or regulation has one or more histopathological features and/or histophysiological features associated with dysfunctional glucose metabolism and/or regulation. The term “histopathological feature” refers to one or more findings in the structure or appearance tissue of a subject which is characteristic of a disease or disorder. Because dysfunctional glucose metabolism and/or regulation can affect the function of numerous cell types, tissues, and organs in a subject, the presence of a histopathological feature of dysfunctional glucose metabolism and/or regulation may be determined by examining a number of tissues using any method known in the art. In some embodiments, the presence of a histopathological feature is determined by examining a sample (e.g., a biopsy, a surgical specimen) of an organ of a subject. In some embodiments, the presence of a histopathological feature is determined by examining an image of a tissue and/or organ of a subject (e.g., radiography, coherence tomography (OCT), funduscopic exams, ultrasounds). In some embodiments, a histopathological feature comprises an abnormality in the cells, tissue, or structure of the kidneys, for example, glomerulomegaly, nephromegaly, glomerular hyperfiltration, albuminuria, mesangiolysis, mesangial matrix expansion, mesangial cell proliferation, thickening of the glomerular basement membrane, podocyte loss, foot process effacement, and hyalinosis of the glomerular arterioles, interstitial fibrosis, tubular atrophy, and tubular hypertrophy. In some embodiments, a histopathological feature comprises an abnormality in the cells, tissue, or structure of the pancreas, for example, insulitis, presence of infiltrating cells, reduced β-cell mass (e.g., β-cell death), and pancreatic fibrosis. In some embodiments, a histopathological feature comprises abnormalities in the cells, tissue, or structure of the retina, for example, microaneurysms, cotton-wool spots, intraretinal hemorrhages, venous beading, microvascular abnormalities, macular thinning, retinal nerve fiber layer thinning, and disorganization of inner retinal layers. In some embodiments, a histopathological feature comprises abnormal cochlear morphology, such as thickening of vessel walls in the basilar membrane and/or stria vascularis, degeneration of the stria vascularis, and degeneration of cochlear outer hair cells. In some embodiments, a histopathological feature comprises peripheral nerve loss (e.g., loss of intradermal nerve fibers, degeneration of myelination, injury of unmyelinated nerves, and axonal atrophy). In some embodiments, a histopathological feature comprises excess body fat (e.g., greater than 25% body fat in women, greater than 20% body fat in men). In some embodiments, a histopathological feature comprises excess deposition of visceral adipose tissue (e.g., in the heart, kidney, liver). In some embodiments, a histopathological feature comprises macrophage accumulation in visceral adipose tissue. The term “pathophysiological feature” refers to one or more findings of functional abnormalities of a tissue of a subject which is characteristic of a disease or disorder. In some embodiments, pathophysiological features are determined from any suitable sample of a subject, for example, a blood/serum or urine sample of the subject. In some embodiments, the pathophysiological feature comprises impaired kidney function. In some embodiments, the pathophysiological feature comprises impaired pancreatic function. In some embodiments, the pathophysiological feature comprises dysglycemia (e.g., hyperglycemia, hypoglycemia). In ^{some embodiments, the pathophysiological feature comprises insulinopenia. In some} embodiments, the pathophysiological feature comprises hyperinsulinemia. In some embodiments, the pathophysiological feature comprises insulin resistance. In some embodiments, the pathophysiological feature comprises hypertriglyceridemia. In some embodiments, the pathophysiological feature comprises atherosclerosis. In some embodiments, the pathophysiological feature comprises neuropathy (e.g., retinal neuropathy, peripheral neuropathy). In some embodiments, the pathophysiological feature comprises impaired gut barrier function. Emerging studies have shown that the gut barrier may be weakened in subjects who consume or have consumed high fat diets for extended periods of time (Zhang, Y., et al. (2023). Frontiers in Nutrition, 10, 1120168). This disruption to the intestinal barrier can allow for the entry of gut bacteria into the circulatory system, which may have a deleterious effect on various tissues and organs (e.g., liver, adipose tissue, pancreas, and immune system) associated with glucose metabolism and/or regulation. Without wishing to be bound by theory, it is believed that entry of bacterial DPP-4 into circulating blood may affect the regulation of blood glucose, for example, via excess cleaving of glucoregulatory peptides (e.g., GLP-1, GLP-2, GIP). In some embodiments, the pathophysiological feature comprises an elevated level of one or more biomarkers associated with glucose metabolism and/or regulation. In some embodiments, the pathophysiological feature comprises a reduced level of one or more biomarkers associated with glucose metabolism and/or regulation. Non-limiting examples of biomarkers associated with glucose metabolism and/or regulation include: glucose, mannose, α- hydroxybutyrate, insulin, anti-glutamic acid decarboxylase (GAD) antibodies, anti-islet antigen 2 (IA2) antibodies, pancreatic islet-cell antibodies, anti-insulin autoantibodies, oxytocin, omentin, endothelin-1, nesfatin-1, irisin, betatrophin, hepatocyte growth factor (HGF), fibroblast growth factor, body mass index, triglycerides, high density lipoprotein (HDL) cholesterol, aspartate aminotransferase (AST), alanine aminotransferase (ALT), GFR, urine albumin, creatinine, blood pressure, cystatin C, amylase, lipase, or any combination thereof. Normal levels of these biomarkers and methods of determining the same are well known in the art, e.g., as described by Menni, C., et al. (2013). Diabetes, 62(12), 4270-4276. In some embodiments, a subject exhibits one or more symptoms of dysfunction of glucose metabolism and/or regulation. Symptoms associated with dysfunction of glucose metabolism and/or regulation include, but are not limited to: increased thirst, frequent urination, dysregulated hunger signals, fatigue, impaired vision, weakness, confusion, nausea or dizziness, ^{headaches, dry mouth, water retention, heart palpitations, abdominal pain, weight loss, weight} gain, edema, spider veins, changes in skin color, or any combination thereof. In some embodiments, a disease or disorder attributed to dysfunctional glucose metabolism and/or regulation comprises: insulin resistance, diabetes mellitus (e.g., diabetes type 1, type 2, gestational), Gaucher’s disease, hemochromatosis, phenylketonuria (PKU), Pompe disease, endocrine disorders, cardiovascular disorders, obesity, metabolic syndrome, and malnutrition. In some embodiments, a subject is at risk of developing dysfunctional glucose metabolism and/or regulation. In some embodiments, a subject has or is suspected of having dysfunctional glucose metabolism and/or regulation. In some embodiments, a subject exhibits one or more signs of symptoms associated with dysfunctional glucose metabolism and/or regulation. In certain embodiments, a method comprises providing (e.g., applying, administering) a composition described herein to a subject having or at risk of having dysfunctional glucose metabolism and/or regulation (e.g., a subject exhibiting one or more signs or symptoms of dysfunctional glucose metabolism and/or regulation). In some embodiments, a subject having or suspected of having dysfunctional glucose metabolism and/or regulation (e.g., exhibiting one or more signs or symptoms of dysfunctional glucose metabolism and/or regulation) has or is suspected of having an abundance of a protease in the gut. In some embodiments, the protease is a human protease. In some embodiments, the protease is a bacterial protease. In some embodiments, the protease is expressed by a bacterium is associated with glucose metabolism and/or regulation. In some embodiments, the bacterium is a species of Bacteroides (e.g., B. vulgatus, B. dorei, B. fragilis, B. massiliensis, B. ovatus, B. thetaiotaomicron (also known as B. theta), B. uniformis, B. stercoris, B. cellulosilyticus, B. xylanisolvens, B. caccae) or Phocaeicola (e.g., P. vulgatus and P. dorei). In some instances, the protease comprises a DPP-4 expressed by B. vulgatus, B. thetaiotaomicron ,and/or B. dorei. In certain embodiments, a method comprises providing (e.g., applying, administering) a composition (e.g., a pharmaceutical composition) comprising a protease inhibitor (e.g., a gliptin and/or a compound described herein) to a subject determined to have or be at risk of having dysfunctional glucose metabolism and/or regulation. In certain embodiments, a method comprises providing (e.g., applying, administering) a composition (e.g., a pharmaceutical composition) comprising a compound of Formula (I) (e.g., a compound shown in Table 1, a compound of Compound No. 26-57), a compound of Formula (II) (e.g., a compound shown in Table 2, a compound of Compound No. 1-24), or a pharmaceutically acceptable salt or other form thereof to a subject determined to have or be at risk of having dysfunctional glucose metabolism and/or regulation. In certain embodiments, a method of determining that a subject has or is at risk of dysfunctional glucose metabolism and/or regulation comprises determining that there is an abundance of a protease in a subject (e.g., relative to a subject having a normal glucose metabolism and/or regulation) for example, in the gut of the subject and/or in a sample of the subject. In some embodiments, the abundance of a protease is an abundance of abacterial protease. In some embodiments, the abundance of a protease is an abundance of bacterial DPP-4 (e.g., DPP-4 expressed by a bacterium of Bacteroides). In certain embodiments, a method comprises determining that a subject has or is at risk of dysfunctional glucose metabolism and/or regulation based on an abundance of a protease in the gut of the subject (e.g., relative to a subject having a normal glucose metabolism and/or regulation), and providing (e.g., applying, administering) a composition (e.g., a pharmaceutical composition) comprising a protease inhibitor (e.g., a gliptin and/or a compound described herein) to the subject. Compositions In one aspect, provided in the present disclosure is a composition (e.g., pharmaceutical composition) comprising a protease inhibitor (e.g., a gliptin and/or a compound described herein), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, and a pharmaceutically acceptable carrier. In some embodiments, a composition (e.g., pharmaceutical composition) comprises a gliptin (e.g., sitagliptin, saxagliptin, teneligliptin, omarigliptin, vildagliptin, or a combination thereof). In some embodiments, a composition (e.g., pharmaceutical composition) comprises a compound of Formula (I) (e.g., a compound shown in Table 1; a compound of Compound No. 26-57) or a pharmaceutically acceptable salt or other form thereof. In some embodiments, a composition (e.g., pharmaceutical composition) comprises a compound of Formula (II) (e.g., a compound shown in Table 2; a compound of Compound No. 1-24) or a pharmaceutically acceptable salt or other form thereof. In some embodiments, the composition (e.g., pharmaceutical composition) described herein, further comprises an additional pharmaceutical agent. In some embodiments, the composition is a pharmaceutical composition. “Pharmaceutical compositions,” as used herein, refer to formulations of protease inhibitors (e.g., a gliptin and/or a compound described herein) in a medium generally accepted in the art for delivery of the protease inhibitors to mammals (e.g., humans). It will be understood that a pharmaceutical composition is a medicament, e.g., a therapeutic and/or prophylactic substance. A pharmaceutical composition (e.g., therapeutic composition, prophylactic composition) may be formulated as, for example, a prescription drug, an over the counter (OTC) medication, a botanical drug, an herbal medicine, a homeopathic agent, a functional food, a pharmaceutical suspension, or any other type of health care product reviewed and approved by a government agency. In some embodiments, a pharmaceutical composition comprises a protease inhibitor (e.g., a gliptin and/or compound described herein) or a pharmaceutically acceptable salt or other form thereof. In certain embodiments, the pharmaceutical compositions described herein comprise a protease inhibitor (e.g., a gliptin or a compound described herein), or a pharmaceutically acceptable salt or other form thereof, and a pharmaceutically acceptable excipient. Pharmaceutical compositions described herein can be prepared by any method known in the art of pharmaceutics. Effective Amounts In some embodiments, a predetermined amount is an effective amount. In certain embodiments, the effective amount is an amount sufficient to induce a therapeutic effect (e.g., a therapeutically effective amount). In some embodiments, a composition (e.g., a pharmaceutical composition) comprises an effective amount of the protease inhibitor or a pharmaceutically acceptable salt or other form thereof. In certain embodiments, the effective amount is a beneficially effective amount. A “beneficial effect” refers to one or more desired biological activities in a subject which are imparted directly or indirectly by a composition described herein. In some embodiments, the desired biological activity comprises modulating the activity of factors which mediate digestion of carbohydrates into glucose. In some embodiments, the desired biological activity comprises modulating factors which mediate absorption of glucose in the gut. In some embodiments, the desired biological activity comprises modulating absorption of glucose into the bloodstream. In some embodiments, the desired biological activity comprises modulating regulation of glucose levels in the blood. In some embodiments, the desired biological activity comprises a restoration of normal glucose homeostasis. In some embodiments, the desired biological activity comprises a restoration of one or more biomarkers associated with dysfunctional glucose metabolism and/or regulation to a normal level. In some embodiments, the desired biological activity comprises a reduction of cholesterol (e.g., LDL cholesterol, HDL cholesterol). In some embodiments, the desired biological activity comprises a reduction of a level of one or more liver enzymes (e.g., AST, ALT) in the blood. In some embodiments, the desired biological activity comprises a reduction in triglyceride levels. In some embodiments, the desired biological activity comprises a restoration of normal blood pressure. In some embodiments, the desired biological activity comprises loss of body fat. In some embodiments, the desired biological activity comprises reduction of gain of body fat. In some embodiments, the desired biological activity comprises a reduction in appetite. In some embodiments, the desired biological activity comprises an increase in appetite. In some embodiments, the desired biological activity comprises improved regulation of food intake (e.g., a reduction in excessive food intake). In certain embodiments, the effective amount is a therapeutically effective amount. A “therapeutic effect” refers to an effect which alleviates (e.g., reduces or eliminates, slows the progression) or treats one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation in a subject. In certain embodiments, a therapeutically effective amount of the protease inhibitor is an amount sufficient to alleviate (e.g., reduces or eliminates, slows the progression of, and/or reduces the severity of) one or more symptoms of dysfunction of glucose metabolism and/or regulation in a subject. In certain embodiments, a therapeutically effective amount of the protease inhibitor is an amount sufficient to restore normal glucose metabolism and/or regulation. In certain embodiments, a therapeutically effective amount of the protease inhibitor is an amount sufficient to modulate glucose absorption and/or insulin secretion in the large intestine (e.g., colon) and/or small intestine of a subject. In certain embodiments, a therapeutically effective amount of the protease inhibitor is an amount sufficient to provide a desired biological activity to a subject. In certain embodiments, the effective amount is a prophylactically effective amount. A “prophylactic effect” refers to an effect which prevents (e.g., delays the onset of) or reduces the likelihood of the development of one or more signs or symptoms of dysfunctional glucose metabolism and/or regulation in a subject. In certain embodiments, a prophylactically effective amount of the protease inhibitor is an amount sufficient to alleviate (e.g., delay or reduce the onset, progression, and/or severity of) one or more symptoms of dysfunction of glucose metabolism and/or regulation in a subject. In certain embodiments, a prophylactically effective amount of the protease inhibitor is an amount sufficient to reduce the risk of a subject ^{developing dysfunction of glucose metabolism and/or regulation. In certain embodiments, a} prophylactically effective amount of the protease inhibitor is an amount sufficient to modulate glucose absorption and/or insulin secretion in the large intestine (e.g., colon) and/or small intestine of a subject. In certain embodiments, the effective amount is an amount effective for inhibiting the activity of a protease by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 98%. Methods of determining inhibition of protease activity are known in the art; for example, a standard protease inhibition assay is described in Example 2. In some embodiments, a therapeutically effective amount of the protease inhibitor is in a range from about 1 mg to 2000 mg (e.g., 1 mg to 10 mg, 1 mg to 50 mg, 1 mg to 100 mg, 10 mg to 50 mg, 10 mg to 100 mg, 50 mg to 100 mg, 100 mg to 150 mg, 100 mg to 200 mg, 150 mg to 200 mg, 200 mg to 250 mg, 250 mg to 300 mg, 300 mg to 400 mg, 400 mg to 500 mg, 500 mg to 750 mg, 750 mg to 1000 mg, 1000 mg to 1250 mg, 1250 mg to 1500 mg, 1500 mg to 2000 mg). Dose ranges as described herein provide guidance for the administration of provided pharmaceutical compositions to an adult. The amount to be administered to, for example, a child or an adolescent can be determined by a medical practitioner or person skilled in the art and can be lower or the same as that administered to an adult. Pharmaceutical compositions can be prepared, packaged, and/or sold in bulk, as a single unit dose, and/or as a plurality of single unit doses. A “unit dose” is a discrete amount of the pharmaceutical composition comprising a predetermined amount of the active ingredient (e.g., protease inhibitor). The amount of the active ingredient is generally equal to the dosage of the active ingredient which would be administered to a subject and/or a convenient fraction of such a dosage, such as one-half or one-third of such a dosage. Formulations In some embodiments, delivering an effective amount of a protease inhibitor (e.g., a gliptin or compound described herein) or a physiologically (e.g., pharmaceutically) acceptable salt thereof to a subject comprises applying a composition (e.g., a pharmaceutical composition) comprising the protease inhibitor via oral, rectal, enteral, parenteral (e.g., intravenous, intramuscular, subcutaneous, intrathecal), nasal, urogenital, topical, and/or intraperitoneal application routes. In certain embodiments, a composition (e.g., a pharmaceutical composition) is formulated for delivery of the protease inhibitor to the gut of a subject. In certain embodiments, a composition (e.g., a pharmaceutical composition) is formulated for delivery of the protease inhibitor to the large intestine of a subject. In certain embodiments, a composition (e.g., a pharmaceutical composition) is formulated for delivery of the protease inhibitor to the colon of a subject. In certain embodiments, a composition (e.g., a pharmaceutical composition) is formulated for delivery of the protease inhibitor to the small intestine of a subject. In certain embodiments, a composition (e.g., a pharmaceutical composition) is formulated for delivery of the protease inhibitor to the small intestine and large intestine of a subject. Pharmaceutical compositions described herein are physiologically acceptable (e.g., pharmaceutically acceptable) for application to human subjects (e.g., for human consumption); for example, pharmaceutical compositions can be understood to be sterile or undergo sterilization during preparation. Pharmaceutical compositions described herein may be formulated in any suitable form for application to a human subject. Preferably, the pharmaceutical composition is suitable for oral application (e.g., ingestion). The inventors have recognized and appreciated that, in cases of oral administration of a protease inhibitor (e.g., a gliptin and/or compound described herein), it may be desirable for an oral dosage form to comprise a controlled release coating to facilitate targeted delivery of the protease inhibitor to a particular location within the gut of a subject (e.g., the colon, the small intestine). In some cases, targeted delivery of the protease inhibitor to a particular location within the gut may enhance treatment efficacy, reduce systemic drug exposure and associated toxicity, and/or improve drug bioavailability. In some embodiments, a composition (e.g., a pharmaceutical composition) comprises a protease inhibitor (e.g., a gliptin and/or compound described herein) or a pharmaceutically acceptable salt or other form thereof, and a targeted delivery facilitating agent. In some embodiments, the targeted delivery facilitating agent comprises one or more materials that dissolve under certain conditions. In some embodiments, a targeted delivery facilitating agent comprises one or more materials that dissolve under certain pH conditions. In some embodiments, the targeted delivery facilitating agent comprises one or more materials that are susceptible to degradation by a microbial organism. In some embodiments, a targeted delivery facilitating agent comprises one or more materials that dissolve under certain pH conditions and/or one or more materials that are susceptible to degradation by a microbial organism. In some embodiments, the pharmaceutical compositions described herein comprise a solid dosage form comprising: a core comprising a protease inhibitor (e.g., a gliptin and/or a ^{compound described herein) in an effective amount; and a controlled release coating applied to} an exterior surface of the core, wherein the controlled release coating is configured to release the inhibitor of the protease in the gut of a subject to whom the solid dosage form is administered. In some embodiments, the core comprises a pH-sensitive material and/or a microbe-sensitive material described herein. In some embodiments, the core comprises one or more nanoparticles (e.g., lipid nanoparticles, polymeric nanoparticles). In some embodiments, the solid dosage form further comprises a carrier (e.g., such that the core is comprised in a carrier). In some embodiments, a solid dosage form comprises a protease inhibitor (e.g., a gliptin and/or a compound described herein) in an effective amount; and a carrier, wherein the protease inhibitor is loaded into the carrier. In some embodiments, the core comprises a tablet, gelcap, capsule, lozenge, sachet, or other suitable solid form. In some embodiments, a core of a solid dosage form comprises a tablet, gelcap, capsule, lozenge, sachet, or other suitable form. In some embodiments, the core of a solid dosage form comprises a tablet, gelcap, capsule, lozenge, sachet, or other suitable form. In some embodiments, a solid dosage form comprises a protease inhibitor (e.g., a gliptin and/or a compound described herein), loaded into an excipient. In some embodiments, a solid dosage form comprises a protease inhibitor (e.g., a gliptin and/or a compound described herein) loaded into a carrier. In some embodiments, a composition (e.g., a pharmaceutical composition) comprises a protease inhibitor (e.g., a gliptin and/or a compound described herein) and a carrier that is not absorbed through an intestinal wall of a subject. In some embodiments, a composition (e.g., a pharmaceutical composition) comprises a protease inhibitor (e.g., a gliptin and/or a compound described herein) and a carrier wherein about 51% to about 99% of which carrier is not absorbed through an intestinal wall of a subject. In some embodiments, a composition comprises a protease inhibitor (e.g., a gliptin and/or a compound described herein) and a carrier wherein about 1%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, or about 49% of which carrier is absorbed into the blood of a subject. In some embodiments, a composition (e.g., a pharmaceutical composition) comprises a protease inhibitor (e.g., a gliptin and/or a compound described herein) and a carrier that targets the protease inhibitor to an intestinal microbiome. In some embodiments, a composition (e.g., a pharmaceutical composition) comprises a protease inhibitor (e.g., a gliptin and/or a compound described herein) and a carrier that specifically targets the protease inhibitor to an intestinal microbiome present in a subject and does not target the protease inhibitor to the blood of the ^{subject. In some embodiments, a composition (e.g., a pharmaceutical composition) comprises a} protease inhibitor (e.g., a gliptin and/or a compound described herein) and a carrier that specifically targets the protease inhibitor to an intestinal location for absorption into the blood. In some embodiments, a carrier that specifically targets a protease inhibitor (e.g., a gliptin and/or a compound described herein) to an intestinal microbiome present in a subject and does not target the protease inhibitor to the blood of the subject comprises a polymer. In some embodiments, a carrier that specifically targets a protease inhibitor (e.g., a gliptin and/or a compound described herein) to an intestinal microbiome comprises a polymer comprising polyvinylpyrrolidone. In some embodiments, a carrier that specifically targets a protease inhibitor (e.g., a gliptin and/or a compound described herein) to an intestinal microbiome comprises a polymer hydrogel, e.g., a polyvinylpyrrolidone (PVP) hydrogel. In some embodiments, a carrier that specifically targets the protease inhibitor (e.g., a gliptin and/or a compound described herein) to an intestinal microbiome comprises a polymer, e.g., a PVP hydrogel loaded with the protease inhibitor. The term “loaded with,” as used herein, refers to an interaction between two molecules, e.g., a polymer and a protease inhibitor (e.g., a gliptin and/or a compound described herein). The interaction can be an interaction based on hydrophilic interaction, e.g., a charge interaction, or a hydrophobic interaction. In some embodiments, a composition (e.g., a pharmaceutical composition) comprising a polymer, e.g., a PVP hydrogel loaded with a protease inhibitor (e.g., a gliptin and/or a compound described herein), targets the protease inhibitor to a location in an intestine. In some embodiments, a composition (e.g., a pharmaceutical composition) comprising a polymer, e.g., a PVP hydrogel loaded with a protease inhibitor (e.g., a gliptin and/or a compound described herein) targets the protease inhibitor to an intestinal location with alkaline pH. For example, a composition (e.g., a pharmaceutical composition) comprising a polymer, e.g., a PVP hydrogel loaded with a protease inhibitor (e.g., a gliptin and/or a compound described herein) may target the protease inhibitor to a distal ileum and/or colon where an alkaline pH decreases hydrogen bonds within the polymer, e.g., PVP hydrogel and hydrogen bonds between the polymer, e.g., PVP hydrogel and the protease inhibitor (e.g., a gliptin and/or a compound described herein) effectuating the release of the protease inhibitor in the distal ileum and/or colon. In some embodiments, a carrier comprising a polymer, e.g., a PVP polymer is associated with a protease inhibitor (e.g., a gliptin and/or a compound described herein) through a linker. In some embodiments, a carrier comprising a polymer, e.g., a PVP polymer is associated with a protease inhibitor (e.g., a gliptin and/or a compound described herein) through a non-digestible linker. In some embodiments, a protease ^{inhibitor (e.g., a gliptin and/or a compound described herein) is dispersed in a polymer, e.g., a} PVP polymer. In some embodiments, a protease inhibitor (e.g., a gliptin and/or a compound described herein) is present in a core, e.g., of a tablet and a polymer, e.g., a PVP polymer surrounds the tablet core. In some embodiments, a composition (e.g., a pharmaceutical composition) comprises a protease inhibitor (e.g., a gliptin and/or a compound described herein) and a carrier that releases the protease inhibitor such that the protease inhibitor is absorbed through an intestinal wall of a subject. In some embodiments, a composition (e.g., a pharmaceutical composition) comprises a protease inhibitor (e.g., a gliptin and/or a compound described herein) and a carrier that releases the protease inhibitor in the small intestine of the subject. In some embodiments, a composition (e.g., a pharmaceutical composition) comprises a protease inhibitor (e.g., a gliptin and/or a compound described herein) and a carrier that releases the protease inhibitor in the ileum of the subject. In some embodiments, a composition (e.g., a pharmaceutical composition) comprises a protease inhibitor (e.g., a gliptin and/or a compound described herein) and a carrier that releases the protease inhibitor in the colon of the subject. In some embodiments, a dosage form comprises a controlled release coating applied to an exterior surface of a core comprising a protease inhibitor (e.g., a gliptin and/or a compound described herein). In some embodiments, the controlled release coating is comprised in a carrier comprising a protease inhibitor (e.g., a gliptin and/or a compound described herein). In some cases, the controlled release coating provides targeted delivery of a protease inhibitor (e.g., a gliptin and/or a compound described herein) (e.g., as comprised in a core) to a desired location within the GI tract, such as one or more portions of the large intestine (e.g., the colon) and/or the small intestine of a subject to whom the pharmaceutical dosage form is administered. In certain embodiments, the controlled release coating is configured to release a protease inhibitor (e.g., a gliptin and/or a compound described herein, as comprised in a core) in the large intestine (e.g., colon) of the subject. In some instances, the controlled release coating is configured to release a protease inhibitor (e.g., a gliptin and/or a compound described herein, as comprised in a core) in the small intestine of the subject. In some embodiments, the controlled release coating consists of a single layer. In some embodiments, the controlled release coating comprises a plurality of layers. The plurality of layers may comprise two, three, four, five, or more layers. In some cases, two or more layers of the plurality of layers comprise the same material. In some cases, two or more layers of the plurality of layers comprise different materials. I^{n some embodiments, one or more layers of the controlled release coating comprise one} or more pH-sensitive materials. A pH-sensitive material generally refers to a material configured to dissolve above or below a threshold pH value. In healthy individuals, pH values are generally low (e.g., 0.95 to 3.5) in the stomach, increase from the proximal small intestine (e.g., 5.5 to 7.0) to the distal ileum (e.g., 6.5 to 7.5), fall in the caecum (e.g., 5.5 to 7.0), and then increase in the colon (e.g., 6.0 to 7.5). In some embodiments, a pH-sensitive material is configured to resist dissolution at the relatively low pH values of the stomach and to dissolve at the relatively high pH values of the colon and/or small intestine. In certain embodiments, a pH-sensitive material is configured to dissolve at a pH of 5.5 or higher, 6.0 or higher, 6.5 higher, 7.0 or higher, or 7.5 or higher. In some embodiments, the one or more pH-sensitive materials comprise a pH-sensitive polymer. In certain cases, a pH-sensitive polymer comprises one or more of the following monomers: methacrylic acid, methyl methacrylate, methyl acrylate, ethyl acrylate, acrylic acid, dimethylaminoethyl methacrylate, butyl methacrylate, and N-isopropylacrylamide. Non-limiting examples of suitable pH-sensitive polymers include copolymers of methacrylic acid and methyl methacrylate, copolymers of methacrylic acid and ethyl acrylate, copolymers of methyl acrylate, methyl methacrylate, and methacrylic acid, an aminoalkyl methacrylate copolymer, cellulose acetate phthalate (“CAP”), hydroxypropyl methylcellulose phthalate (“HPMCP”), hydroxypropyl methylcellulose acetate succinate (“HPMC-AS”), poly(N-isopropylacrylamide) (“PNI-PAM”), EUDRAGIT^® S, EUDRAGIT^® FS, EUDRAGIT^® L, and Kollicoat^® MAE 100P. In some cases, one or more layers of the controlled release coating comprise a microbe- sensitive material. In some cases, a microbe-sensitive material is susceptible to degradation by one or more microbial organisms residing in a portion of the GI tract (e.g., the colon). Non- limiting examples of suitable microbe-sensitive materials include amylose, lactulose, amylopectin, pectin, guar gum, locust bean gum, inulin, chitosan, arabinoxylans, agave fructans, alginate, chondroitin sulfate, dextran, and cyclodextrin. In certain embodiments, the controlled release coating comprises a layer comprising a pH-sensitive material and a microbe-sensitive material. In certain embodiments, the controlled release coating comprises one or more layers comprising a pH-sensitive material and one or more layers comprising a microbe-sensitive material. In certain embodiments, the controlled release coating comprises one or more layers comprising a first pH-sensitive material and one or more layers comprising a second pH-sensitive material. In some instances, the controlled release coating comprises one, two, three, four, five, or more pH-sensitive materials. In certain ^{embodiments, the controlled release coating comprises one or more layers comprising a first} microbe-sensitive material and one or more layers comprising a second microbe-sensitive material. In some instances, the controlled release coating comprises one, two, three, four, five, or more microbe-sensitive materials. In some cases, the controlled release coating comprises one or more hydrophilic layers and one or more lipophilic layers. In some cases, the controlled release coating comprises one or more layers formed from an aqueous solution and one or more layers formed from an organic solution. In certain embodiments, the controlled release coating comprises a rupturable film. In certain embodiments, the controlled release coating comprises a hydrogel plug configured to swell upon exposure to moisture and rupture the coating. In some instances, the hydrogel plug may be covered by a cap comprising a pH-sensitive material and/or a microbe-sensitive material. In solid dosage forms comprising a core, components of the core (e.g., a protease inhibitor) may be mixed with at least one inert, physiologically (e.g., pharmaceutically) acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or (a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, (b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, and acacia, (c) humectants such as glycerol, (d) disintegrating agents such as agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, (e) solution retarding agents such as paraffin, (f) absorption accelerators such as quaternary ammonium compounds, (g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, (h) absorbents such as kaolin and bentonite clay, and (i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In some embodiments, a solid dosage form may include a buffering agent. In some aspects, a dosage form (e.g., a pharmaceutical dosage form) comprises a protease inhibitor (e.g., a gliptin and/or a compound described herein) described herein and a liquid or gel carrier. In some embodiments, the liquid or gel carriers include water, saline solutions, alcohol solutions, dextrose solutions, glycerol solutions, and oils, including but not limited to petroleum oil (e.g., mineral oil), vegetable oil (e.g., peanut oil, soybean oil, sesame oil), animal oil, and oil of synthetic origin. In some embodiments, a dosage form (e.g., a solid dosage form, an oral dosage form) comprises one or more acceptable excipients. In some cases, the one or more acceptable excipients are physiologically acceptable excipients. In some embodiments, the physiologically acceptable excipients comprise one or more physiologically acceptable carriers, buffers, salts, ^{inert diluents or filling agents, binders, stabilizers, emulsifiers, disintegrants, diluents, lubricants,} additives, preservatives, taste maskers, colorants, adjuvants, dispersing and/or granulating agents, surface active agents and/or, oils, and/or other agents. In some embodiments, a physiologically acceptable excipient is a pharmaceutically acceptable excipient. In some embodiments, a dosage form (e.g., a solid dosage form, an oral dosage form) comprises one or more acceptable excipients. In some cases, the one or more acceptable excipients are physiologically acceptable excipients. In some embodiments, the physiologically acceptable excipients comprise one or more physiologically acceptable carriers, buffers, salts, inert diluents or filling agents, binders, stabilizers, emulsifiers, disintegrants, diluents, lubricants, additives, preservatives, taste maskers, colorants, adjuvants, dispersing and/or granulating agents, surface active agents and/or, oils, and/or other agents. In some embodiments, a physiologically acceptable excipient is a pharmaceutically acceptable excipient. Other dosage forms are also contemplated herein. In certain embodiments, the pharmaceutical dosage form is formulated as a solution, emulsion, or suspension for oral administration. In certain embodiments, the pharmaceutical dosage form is formulated as an aqueous solution, an alcoholic solution, an emulsion, a gel, a cream, and/or an ointment for rectal administration. In certain embodiments, rectal administration is achieved through the use of an enema, a suppository, a tube, or an aerosol with an attachment that is inserted into the anus. In certain embodiments, the pharmaceutical dosage form is formulated as an injection for intraperitoneal, intramuscular, subcutaneous, intravenous, or intrathecal administration. In some embodiments, the pharmaceutical composition is formulated as a spray (e.g., for nasal administration). Kits Also encompassed by the disclosure are kits (e.g., pharmaceutical packs). The kits provided may comprise a pharmaceutical composition or compound described herein and a container (e.g., a vial, ampule, bottle, syringe, and/or dispenser package, or other suitable container). In some embodiments, provided kits may optionally further include a second container comprising a pharmaceutical excipient for dilution or suspension of a pharmaceutical composition or compound described herein. In some embodiments, the pharmaceutical composition or compound described herein provided in the first container and the second container are combined to form one unit dosage form. In one aspect, provided herein a kit comprising: a compound described herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, or a pharmaceutical composition provided herein; and instructions for using the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, or the pharmaceutical composition. Thus, in certain embodiments, provided are kits including a first container comprising a compound or pharmaceutical composition described herein. In certain embodiments, the kits are useful for treating a disease (e.g., metabolic disorder) in a subject in need thereof. In certain embodiments, the kits are useful for preventing a disease (e.g., metabolic disorder) in a subject in need thereof. In certain embodiments, the kits are useful for reducing the risk of developing a disease (e.g., metabolic disorder) in a subject in need thereof. In certain embodiments, the kits are useful for inhibiting the activity of a protease in a subject or cell. In certain embodiments, a kit described herein further includes instructions for using the kit. A kit described herein may also include information as required by a regulatory agency such as the U.S. Food and Drug Administration (FDA). In certain embodiments, the information included in the kits is prescribing information. In certain embodiments, the kits and instructions provide for treating a disease (e.g., metabolic disorder) in a subject in need thereof. In certain embodiments, the kits and instructions provide for preventing a disease (e.g., metabolic disorder) in a subject in need thereof. In certain embodiments, the kits and instructions provide for reducing the risk of developing a disease (e.g., metabolic disorder) in a subject in need thereof. In certain embodiments, the kits and instructions provide for inhibiting the activity of a protease in a subject or cell. A kit described herein may include one or more additional pharmaceutical agents described herein as a separate composition. Methods of Use In some aspects, provided herein are methods comprising providing (e.g., administering, applying) a composition comprising a protease inhibitor (e.g., a gliptin and/or a compound described herein) to a subject in need thereof. In some embodiments, a method comprises providing a gliptin (e.g., sitagliptin, saxagliptin, teneligliptin, omarigliptin, vildagliptin, or a combination thereof) or a pharmaceutically acceptable salt or other form thereof to a subject in need thereof. In some embodiments, a method comprises providing a composition (e.g., pharmaceutical composition) comprises a compound of Formula (I) (e.g., a compound shown in Table 1; a compound of Compound No. 26-57) or a pharmaceutically acceptable salt or other form thereof to a subject in need thereof. In some embodiments, a method comprises providing a compound of Formula (II) (e.g., a compound shown in Table 2; a compound of Compound No. 1-24) or a pharmaceutically acceptable salt or other form thereof to a subject in need thereof. In some embodiments, providing a composition to a subject comprises applying the composition to the subject. In some embodiments, providing a composition to a subject comprises administering the composition to the subject. In some embodiments, methods provided herein comprise a method of providing one or more beneficial effects to a subject (e.g., a subject exhibiting one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation). In some embodiments, methods provided herein comprise a method of providing one or more beneficial effects to a subject (e.g., a subject exhibiting one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation), the method comprising providing a composition (e.g., a pharmaceutical composition) described herein to the subject. In some embodiments, methods provided herein comprise a method of providing one or more beneficial effects to a subject (e.g., a subject exhibiting one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation), the method comprising administering a composition (e.g., a pharmaceutical composition) described herein to the subject. In some embodiments, methods provided herein comprise a method of providing one or more beneficial effects to a subject (e.g., a subject exhibiting one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation), the method comprising providing composition (e.g., a pharmaceutical composition) described herein to the subject, for example, along with instructions for administering the composition (e.g., the pharmaceutical composition) to the subject (e.g., self-administration). In some embodiments, methods provided herein comprise a method of providing one or more prophylactic effects to a subject having or at risk of developing a disease or disorder associated with dysfunction of glucose metabolism and/or regulation (e.g., a subject exhibiting one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation). In some embodiments, methods provided herein comprise a method of providing one or more prophylactic effects to a subject having or at risk of developing a disease or disorder associated with dysfunction of glucose metabolism and/or regulation (e.g., a subject exhibiting one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation), the method comprising providing a composition (e.g., a pharmaceutical composition) described herein to the subject. In some embodiments, methods provided herein comprise a method of providing one or ^{more prophylactic effects to a subject having or at risk of developing a disease or disorder} associated with dysfunction of glucose metabolism and/or regulation (e.g., a subject exhibiting one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation), the method comprising administering a composition (e.g., a pharmaceutical composition) described herein to the subject. In some embodiments, methods provided herein comprise a method of providing one or more prophylactic effects to a subject having or at risk of developing a disease or disorder associated with dysfunction of glucose metabolism and/or regulation (e.g., a subject exhibiting one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation), the method comprising providing composition (e.g., a pharmaceutical composition) described herein to the subject, for example, along with instructions for administering the composition (e.g., the pharmaceutical composition) to the subject (e.g., self-administration). In some embodiments, methods provided herein comprise a method of providing one or more therapeutic effects to a subject having or at risk of developing a disease or disorder associated with dysfunction of glucose metabolism and/or regulation (e.g., a subject exhibiting one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation). In some embodiments, methods provided herein comprise a method of providing one or more therapeutic effects to a subject having or at risk of developing a disease or disorder associated with dysfunction of glucose metabolism and/or regulation (e.g., a subject exhibiting one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation), the method comprising providing a composition (e.g., a pharmaceutical composition) described herein to the subject. In some embodiments, methods provided herein comprise a method of providing one or more therapeutic effects to a subject having or at risk of developing a disease or disorder associated with dysfunction of glucose metabolism and/or regulation (e.g., a subject exhibiting one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation), the method comprising administering a composition (e.g., a pharmaceutical composition) described herein to the subject. In some embodiments, methods provided herein comprise a method of providing one or more therapeutic effects to a subject having or at risk of developing a disease or disorder associated with dysfunction of glucose metabolism and/or regulation (e.g., a subject exhibiting one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation), the method comprising providing composition (e.g., a pharmaceutical composition) described herein to the subject, for example, along with instructions for administering the composition (e.g., the pharmaceutical composition) to the subject (e.g., self-administration). In some embodiments, methods provided herein comprise methods of treating (e.g., ^{providing one or more therapeutic effects) to a subject having or suspected of having a disease} or disorder associated with dysfunction of glucose metabolism and/or regulation (e.g., a subject exhibiting one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation). In some embodiments, methods provided herein comprise methods of treating (e.g., providing one or more therapeutic effects) to a subject having or at risk of developing a disease or disorder associated with dysfunction of glucose metabolism and/or regulation (e.g., a subject exhibiting one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation), the method comprising providing a composition (e.g., a pharmaceutical composition) to the subject. In some embodiments, methods provided herein comprise methods of treating (e.g., providing one or more therapeutic effects) to a subject having or at risk of developing a disease or disorder associated with dysfunction of glucose metabolism and/or regulation (e.g., a subject exhibiting one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation), the method comprising administering a composition (e.g., a pharmaceutical composition) to the subject. In some embodiments, methods provided herein comprise methods of treating (e.g., providing one or more therapeutic effects) to a subject having or at risk of developing a disease or disorder associated with dysfunction of glucose metabolism and/or regulation (e.g., a subject exhibiting one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation), the method comprising providing a composition (e.g., a pharmaceutical composition) to the subject, for example, along with instructions for administering the composition (e.g., the pharmaceutical composition) to the subject (e.g., self-application, self-administration). Subjects In some embodiments, a subject has, is suspected of having, or is at risk of developing a dysfunction of glucose metabolism and/or regulation. In some embodiments, a subject exhibits one or more signs or symptoms of a dysfunction of glucose metabolism and/or regulation. In some embodiments, a subject at risk of developing a dysfunction of glucose metabolism and/or regulation is a subject that has been identified to be at risk of a dysfunction of glucose metabolism and/or regulation by a qualified healthcare professional. In some embodiments, a subject at risk of developing a dysfunction of glucose metabolism and/or regulation is a subject that has been identified to be at risk of the dysfunction of glucose metabolism and/or regulation using biomarker evaluation. In some embodiments, a subject at risk of developing a dysfunction of glucose metabolism and/or regulation has a lifestyle having one or more factors associated with increased risk of developing a dysfunction of glucose metabolism and/or regulation. In some embodiments, the subject has a genetic predisposition for a dysfunction of glucose metabolism and/or regulation. In some embodiments, the subject is aged over 45 years. In some embodiments, the subject has excess abdominal fat (e.g., visceral fat). In some embodiments, the subject has excess body fat. In some embodiments, the subject has high blood pressure. In some embodiments, the subject has high blood cholesterol. In some embodiments, the subject has a sedentary lifestyle. In some embodiments, the subject has a history of consuming a diet associated with an increased risk of a dysfunction of glucose metabolism and/or regulation for an extended period of time. In some embodiments, a diet associated with an increased risk of glucose metabolism and/or regulation is a high fat diet. In some embodiments, a high fat diet comprises 30% or more (e.g., 30-35%, 30-40%, 35-40%, 35-45%, 40-50%, or 45% more) calories from fat. In some embodiments, the extended period of time comprises 6 months or more, 1 year or more, 2 years or more, 3 years or more, 4 years or more, 5 years or more, 10 years or more, 20 years or more, or 30 years or more. In some embodiments, the subject has or has had an illness linked to dysfunction of glucose metabolism and/or regulation (e.g., endocrinopathies, Cushing’s syndrome, acromegaly, pheochromocytoma, glucagonoma, hyperthyroidism, pancreatitis, hemochromatosis, cystic fibrosis, cancer). In some embodiments, the subject is taking or has received an extended course of certain medications known to have side effects related to dysfunction of glucose metabolism and/or regulation. Non-limiting examples of these medications include glucocorticoids, diazoxide, thiazides, β2-receptor agonists, nonselective β-adrenergic antagonists, dilantin, growth hormone, thyroid hormone, somatostatin, estradiol, levonorgestrel, glucagon, anti- retrovirals, nicotinic acid, streptozocin, antipsychotics, and immune checkpoint inhibitors. In some embodiments, the subject has been infected by a virus which has been linked to dysfunctions of glucose metabolism and/or regulation (e.g., cytomegalovirus, adenovirus, Coxsackie virus B, mumps, hepatitis C). In some embodiments, a subject has, is suspected of having, or is at risk of developing a dysfunction of glucose metabolism and/or regulation. In some embodiments, the subject exhibits one or more signs or symptoms of a dysfunction of glucose metabolism and/or regulation. In some embodiments, the subject has not received a treatment which modulates glucose metabolism and/or regulation. In some embodiments, the subject has received a treatment which modulates glucose metabolism and/or regulation. In some embodiments, the subject is refractory ^{to another treatment which modulates glucose metabolism and/or regulation. In some} embodiments, the subject is concomitantly receiving another treatment which modulates glucose metabolism and/or regulation. In some embodiments, the compositions and methods described herein are provided to a subject. In some embodiments, the subject is a mammalian subject. In certain embodiments, the subject is a non-human animal subject. Examples of suitable non-human animal subjects include, but are not limited to, non-human primates, dogs, cats, sheep, cows, pigs, horses, mice, rats, and rabbits. In some embodiments, the subject is a human subject. In certain embodiments, the subject is male. In certain embodiments, the subject is female. The subject may be from any geographical location. In certain embodiments, the subject is from North America (e.g., the United States), Asia (e.g., China, South Korea), Europe (e.g., Italy), and/or South America (e.g., Ecuador). The subject may be of any age. In certain embodiments, the subject is a child (e.g., 17 years old or younger). In certain embodiments, the subject is an adult (e.g., 18 years old or older). In some embodiments, the subject has an age in a range from 1-5 years old, 1-7 years old, 1-10 years old, 1-15 years old, 1-17 years old, 1-18 years old, 1-21 years old, 1-50 years old, 1- 70 years old, 1-100 years old, 2-7 years old, 2-10 years old, 2-15 years old, 2-17 years old, 2-18 years old, 2-21 years old, 2-50 years old, 2-70 years old, 2-100 years old, 5-10 years old, 5-15 years old, 5-17 years old, 5-18 years old, 5-21 years old, 5-50 years old, 5-70 years old, 5-100 years old, 10-15 years old, 10-17 years old, 10-18 years old, 10-21 years old, 10-50 years old, 10-70 years old, 10-100 years old, 15-21 years old, 15-50 years old, 15-70 years old, 15-100 years old, 18-50 years old, 18-70 years old, 18-100 years old, 21-50 years old, 21-70 years old, 21-100 years old, 50-70 years old, 50-100 years old, or 70-100 years old. Methods of Administration In some embodiments, a composition (e.g., a pharmaceutical composition) described herein is provided (e.g., administered) chronically. In some embodiments, the composition (e.g., the pharmaceutical composition) is administered chronically. In certain embodiments, the composition (e.g., the pharmaceutical composition) is provided (e.g., administered) over a period of at least 1 month, at least 3 months, at least 6 months, at least 9 months, at least 1 year, at least 3 years, at least 5 years, at least 10 years, or at least 20 years. In certain embodiments, the composition (e.g., the pharmaceutical composition) is provided over a period of 1 to 3 months, 1 to 6 months, 1 to 9 months, 1 month to 1 year, 1 month to 3 years, 1 month to 5 years, 1 month to 10 years, 1 month to 20 years, 3 to 6 months, 3 to 9 months, 3 months to 1 year, 3 months to 3 years, 3 months to 5 years, 3 months to 10 years, 3 months to 20 years, 6 to 9 months, 6 months to 1 year, 6 months to 3 years, 6 months to 5 years, 6 months to 10 years, 6 months to 20 years, 9 months to 1 year, 9 months to 3 years, 9 months to 5 years, 9 months to 10 years, 9 months to 20 years, 1 to 3 years, 1 to 5 years, 1 to 10 years, 1 to 20 years, 3 to 5 years, 3 to 10 years, 3 to 20 years, 5 to 10 years, 5 to 20 years, or 10 to 20 years. In some embodiments, a composition (e.g., the pharmaceutical composition) is provided to a subject daily, weekly, monthly, or at shorter or longer time intervals. In some embodiments, a composition (e.g., a pharmaceutical composition) is administered to a subject until one or more signs or symptoms of a dysfunction of glucose metabolism and/or regulation (e.g., a disease associated with dysfunction of glucose metabolism and/or regulation) are alleviated (e.g., until an episode ends and the subject enters remission). In some embodiments, a pharmaceutical composition (e.g., a therapeutic pharmaceutical composition) is provided (e.g., administered) to a subject in an amount sufficient to alleviate (e.g., reducing or eliminating, slowing the progression) or treat one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation. In some embodiments, a composition (e.g., a prophylactic pharmaceutical composition) is provided (e.g., administered) to a subject in an effective amount, for example in an amount sufficient to prevent (e.g., delays the onset of) or reduce the likelihood of one or more signs or symptoms of a dysfunction of glucose metabolism and/or regulation. In some embodiments, a composition (e.g., a prophylactic pharmaceutical composition) is provided (e.g., administered) to a subject in an amount sufficient to reduce a risk of a subject developing a dysfunction of glucose metabolism and/or regulation. In some embodiments, a composition is provided (e.g., administered) to a subject in an amount sufficient to provide a desired effect in a subject. In some embodiments, a desired effect comprises one or more beneficial effects (e.g., a beneficial effect described herein). In some embodiments, a desired effect comprises loss of body fat and/or prevent or slow accumulation of body fat. In some embodiments, a subject desiring to lose body fat exhibits one or more symptoms of or risk factors for dysfunction of glucose metabolism and/or regulation. In some embodiments, a subject desiring to lose body fat does not exhibit symptoms of or risk factors for dysfunction of glucose metabolism and/or regulation. In some aspects, the pharmaceutical dosage forms described herein can be administered alone e.g., as monotherapies. In some aspects, the pharmaceutical dosage forms described herein can be administered concurrently with, prior to, or subsequent to one or more additional pharmaceutical agents, which may be useful as, e.g., combination therapies. Pharmaceutical agents include therapeutically active agents. Pharmaceutical agents also include prophylactically active agents. Pharmaceutical agents include small organic molecules such as drug compounds (e.g., compounds approved for human or veterinary use by the U.S. Food and Drug Administration as provided in the Code of Federal Regulations (CFR)), peptides, proteins, biologics (e.g., monoclonal antibodies), carbohydrates, monosaccharides, oligosaccharides, polysaccharides, nucleoproteins, mucoproteins, lipoproteins, synthetic polypeptides or proteins, small molecules linked to proteins, glycoproteins, steroids, nucleic acids, DNAs, RNAs, nucleotides, nucleosides, oligonucleotides, antisense oligonucleotides, lipids, hormones, vitamins, and cells. In certain embodiments, the additional pharmaceutical agent is a pharmaceutical agent useful for treating and/or preventing a disease (e.g., a disease associated with a dysfunction of glucose metabolism and/or regulation). In some embodiments, the pharmaceutical agent comprises administration of insulin, alpha-glucosidase inhibitors, biguanides (e.g., metformin), dopamine-2 agonists, sodium-glucose transporter inhibitors, sulfonylureas, thiazolidinediones, aspirin, statins, niacin, cholesterol absorption inhibitors, PCSK9 inhibitors, anti-hypertensives, orlistat, phentermine-topiramate, naltrexone-bupropion, liraglutide, semaglutide, setmelanotide, levothyroxine, hormone replacement therapy, or a combination or two or more thereof. Each additional pharmaceutical agent may be administered at a dose and/or on a time schedule determined for that pharmaceutical agent. The additional pharmaceutical agents may also be administered together with each other and/or with the compound or composition described herein in a single dose or composition or administered separately in different doses or compositions. The particular combination to employ in a regimen will take into account compatibility of the compound described herein with the additional pharmaceutical agent(s) and/or the desired therapeutic and/or prophylactic effect to be achieved. In general, it is expected that the additional pharmaceutical agent(s) in combination be utilized at levels that do not exceed the levels at which they are utilized individually. In some embodiments, the levels utilized in combination will be lower than those utilized individually. In some embodiments, a method comprises providing (e.g., applying, administering) a composition described herein to a subject. In some embodiments, a method comprises inducing one or more prophylactic effects ^{in a subject. In some embodiments, inducing one or more prophylactic effects in a subject} comprises administering a pharmaceutical composition described herein to a subject. In some embodiments, a method comprises inducing one or more therapeutic effects in a subject. In some embodiments, inducing one or more therapeutic effects in a subject comprises administering a pharmaceutical composition described herein to a subject. In some embodiments, a method comprises treating a subject. In some embodiments, the method of treating a subject comprises administering a pharmaceutical composition (e.g., a therapeutic composition) described herein to the subject. In some embodiments, providing a composition to the subject modulates a level of protease (e.g., DPP-4) activity in the subject (e.g., in the gut of the subject) to alleviate one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation. In some embodiments, providing a composition to the subject modulates a level of protease (e.g., DPP-4) activity in the subject (e.g., in the gut of the subject) to reduce the risk of developing dysfunction of glucose metabolism and/or regulation. In some embodiments, providing a composition to the subject modulates a level of bacterial protease (e.g., bacteria; DPP-4) activity in the subject (e.g., in the gut of the subject) to alleviate one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation. In some embodiments, providing a composition to the subject modulates a level of bacterial protease (e.g., bacteria; DPP-4) activity in the subject (e.g., in the gut of the subject) to reduce the risk of developing dysfunction of glucose metabolism and/or regulation. In some embodiments, providing a composition to the subject modulates a level of human protease (e.g., human DPP-4) activity in the subject (e.g., in the gut of the subject) to alleviate one or more signs or symptoms of dysfunction of glucose metabolism and/or regulation, and/or to reduce the risk of developing dysfunction of glucose metabolism and/or regulation. In some embodiments, providing a composition to the subject modulates a level of human protease (e.g., human DPP-4) activity in the subject (e.g., in the gut of the subject) to reduce the risk of developing dysfunction of glucose metabolism and/or regulation. In some embodiments, modulating the level of protease activity comprises modulating the level of bacterial protease activity. In some embodiments, modulating the level of bacterial protease activity comprises reducing (e.g., inhibiting) the activity of the bacterial protease. In some embodiments, modulating the level of bacterial protease activity comprises reducing (e.g., inhibiting) the activity of the bacterial protease by 5% or more (e.g., by 10% or more, 15% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% ^{or more, 90% or more, 95% or more, 99% or more) relative to the activity of the bacterial} protease prior to providing the composition to the subject. In some embodiments, modulating the level of bacterial protease activity comprises reducing (e.g., inhibiting) the activity of bacterial DPP-4. In some embodiments, modulating the level of bacterial DPP-4 activity comprises reducing (e.g., inhibiting) the activity of the bacterial DPP-4 by 5% or more (e.g., by 10% or more, 15% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 95% or more, 99% or more) relative to the activity of the bacterial DPP-4 protease prior to providing the composition to the subject. In some embodiments, modulating the level of protease activity comprises modulating the level of human protease activity. In some embodiments, modulating the level of bacterial protease activity comprises reducing (e.g., inhibiting) the activity of the human protease. In some embodiments, modulating the level of human protease activity comprises reducing (e.g., inhibiting) the activity of the bacterial protease by 5% or more (e.g., by 10% or more, 15% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 95% or more, 99% or more) relative to the activity of the human protease prior to providing the composition to the subject. In some embodiments, modulating the level of human protease activity comprises reducing (e.g., inhibiting) the activity of human DPP-4. In some embodiments, modulating the level of human DPP-4 activity comprises reducing (e.g., inhibiting) the activity of the human DPP-4 by 5% or more (e.g., by 10% or more, 15% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 95% or more, 99% or more) relative to the activity of the human DPP-4 prior to providing the composition to the subject. In some embodiments, modulating the level of protease activity comprises modulating the level of activity of a bacterial protease and the level of activity of a human protease. In some embodiments, modulating the level of protease activity comprises reducing (e.g., inhibiting) the activity of a bacterial protease and reducing the activity of a human protease. In some embodiments, modulating the level of protease activity comprises reducing (e.g., inhibiting) the activity of the bacterial protease by 5% or more (e.g., by 10% or more, 15% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 95% or more, 99% or more) relative to the activity of the bacterial protease prior to providing the composition to the subject and reducing (e.g., inhibiting) the activity of the human protease by 5% or more (e.g., by 10% or more, 15% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 95% or more, ^{99% or more) relative to the activity of the human protease prior to providing the composition to} the subject. In some embodiments, modulating the level of protease activity comprises modulating the level of activity of bacterial DPP-4 and the level of activity of human DPP-4. In some embodiments, modulating the level of protease activity comprises reducing (e.g., inhibiting) the activity of bacterial DPP-4 and reducing the activity of human DPP-4. In some embodiments, modulating the level of protease activity comprises reducing (e.g., inhibiting) the activity of the bacterial DPP-4 by 5% or more (e.g., by 10% or more, 15% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 95% or more, 99% or more) relative to the activity of the bacterial DPP-4 protease prior to providing the composition to the subject and reducing (e.g., inhibiting) the activity of the human DPP-4 by 5% or more (e.g., by 10% or more, 15% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 95% or more, 99% or more) relative to the activity of the human DPP-4 protease prior to providing the composition to the subject. Methods of Determining Protease Abundance in Samples In some aspects, a composition provided herein is provided to a subject who has been determined to have an abundance of a bacterial protease relative to the level in a subject without a dysfunction of glucose metabolism and/or regulation. In some aspects, a method of treating dysfunctions of glucose metabolism and/or regulation (e.g., diabetes, obesity and/or metabolic syndrome) comprises determining an abundance of a bacterial protease in a sample obtained from a subject and delivering a therapeutically effective amount of an inhibitor of the bacterial protease to the large intestine (e.g., colon) and/or small intestine of the subject. The bacterial protease may be any bacterial protease described herein. The inhibitor of the bacterial protease may be any protease inhibitor described herein. The subject may be any subject described herein. In some embodiments, determining an abundance of a bacterial protease in a sample obtained from a subject comprises obtaining the sample from the subject. In certain embodiments, the sample represents characteristics of the subject’s GI tract. In some instances, the sample is a fecal sample. In some instances, the sample is a gastrointestinal sample taken from the GI tract (e.g., the lower GI tract, the upper GI tract). The gastrointestinal sample may be obtained during any suitable procedure, including but not limited to colonoscopy, endoscopy, swabbing, or brushing a part of the GI tract. In some instances, the sample is a serum sample. In some embodiments, determining the abundance of the bacterial protease comprises determining an abundance of one or more genes present in the sample from the subject. In some embodiments, determining the abundance of one or more genes present in the sample comprises extracting DNA and/or RNA from at least a portion of the sample. Any nucleic acid extraction method known in the art may be used. In some embodiments, determining the abundance of one or more genes present in the sample further comprises amplifying at least a portion of the DNA and/or RNA to produce a plurality of amplicons. Any nucleic acid amplification method known in the art may be used. Non-limiting examples of suitable nucleic acid amplification methods include polymerase chain reaction (PCR) and isothermal amplification methods (e.g., loop- mediated isothermal amplification (LAMP), rolling circle amplification (RCA), nucleic acid sequence-based amplification (NASBA)). In some embodiments, determining the abundance of one or more genes present in the sample comprises performing a quantitative nucleic acid amplification method. A non-limiting example of a suitable quantitative nucleic acid amplification method is quantitative PCR (qPCR). In some embodiments, determining the abundance of one or more genes present in the sample further comprises sequencing one or more amplicons. Any suitable nucleic acid sequencing method may be used. In certain embodiments, the nucleic acid sequencing method is a long-read sequencing method. In certain embodiments, the nucleic acid sequencing method is a short-read sequencing method. In some embodiments, the nucleic acid sequencing method is a next-generation sequencing method. In some embodiments, the nucleic acid sequencing method is performed using an Illumina, Pacific Biosciences, Oxford Nanopore, and/or Roche 454 sequencing platform. In some embodiments, determining the abundance of one or more genes present in a sample comprises sequencing at least a portion of 16S ribosomal RNA (rRNA) of microbes present in the sample (e.g., performing 16S rRNA gene amplicon (16S) sequencing). In some cases, performing 16S sequencing comprises amplifying at least a portion of one or more regions of the 16S rRNA genome of microbes present in the sample to produce a plurality of amplicons. Any nucleic acid amplification method (e.g., PCR) may be used. In some embodiments, the one or more regions of the 16S rRNA genome comprise at least one hypervariable region (e.g., V4, V3-V4, V1-V2). In some cases, performing 16S sequencing further comprises sequencing one or more amplicons of the plurality of amplicons. Any suitable nucleic acid sequencing method may be used. In some embodiments, determining the abundance of one or more genes present in a ^{sample comprises performing shotgun metagenomic sequencing to sequence the metagenomic} content of the sample. In some cases, shotgun metagenomic sequencing methods comprise extracting DNA from a sample, fragmenting the extracted DNA into DNA fragments, and sequencing the DNA fragments. Any suitable nucleic acid sequencing method may be used. In some cases, the resulting sequences of the DNA fragments may be analyzed to identify microbes present in the sample. In some embodiments, determining the abundance of one or more genes present in a sample comprises determining the level of one or more gene products (e.g., enzymes) in a sample. The level of the one or more gene products may be determined according to any method known in the art, including but not limited to an enzyme-linked immunosorbent assay (ELISA) and other antibody-based assays, and liquid chromatography-mass spectrometry (LC-MS)-based proteomics and other protein-based quantification assays. In some embodiments, determining the abundance of one or more genes present in a sample comprises determining the level of one or more molecules that directly or indirectly interact with one or more gene products (e.g., enzymes) in a metabolic pathway (e.g., as a substrate or a product). The level of the one or more molecules (e.g., substrates, products) may be determined according to any method known in the art, including but not limited to high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), gas chromatography-mass spectrometry (GC- MS), and fluorescence-based assays. In some embodiments, a method comprises determining the abundance of a bacterial protease and delivering an effective amount (e.g., a therapeutically effective amount, a prophylactically effective amount) of an inhibitor of the bacterial protease to the subject. In some embodiments, a method comprises determining the abundance of a bacterial protease and delivering a therapeutically effective amount of an inhibitor of the bacterial protease to the GI tract of the subject. In some embodiments, a method comprises determining the abundance of a bacterial protease and delivering a therapeutically effective amount of an inhibitor of the bacterial protease to the large intestine (e.g., colon) and/or small intestine of the subject. According to some embodiments, a method comprises determining, if the abundance of the bacterial protease is higher or lower than a threshold value, that a therapeutically effective amount of an inhibitor of the bacterial protease should be administered. In some cases, the threshold value may be determined based on the level of the bacterial protease in one or more healthy individuals (e.g., individuals who do not exhibit symptoms of or have risk factors for dysfunctions of glucose metabolism and/or regulation). In some cases, the threshold value may ^{be determined by identifying an optimal discriminatory boundary between a first population of} individuals having one or more symptoms of or risk factors for dysfunctions of glucose metabolism and/or regulation and a second population of healthy individuals. Administering the therapeutically effective amount of the inhibitor of the bacterial protease may be performed according to any method described herein. EMBODIMENTS Embodiment 1. A compound of Formula (I):

or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein: R^b is optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted acyl, optionally wherein one or more backbone carbon atoms in the optionally substituted alkyl are independently replaced with –O– or –S-; Each instance of R¹¹ is independently hydrogen, optionally substituted alkyl, optionally substituted acyl, or a nitrogen protecting group; R^c and R^d are each independently hydrogen, optionally substituted alkyl, halo, -OR^x, or optionally wherein R^c and R^d are joined together to form an optionally substituted C1-6 carbocycle; R^x is hydrogen, optionally substituted alkyl, or an oxygen protecting group; R¹² is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkynyl, optionally substituted acyl, or azido; and n is 0, 1, or 2; provided that the compound is not of the formula:

. Embodiment 2. The compound of embodiment 0, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein the compound is of Formula (I-a-I):

wherein R¹² is optionally substituted C1-6 alkynyl, optionally substituted C1-6 heteroalkynyl, optionally substituted acyl, or azido. Embodiment 3. The compound of embodiment 0 or 0, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein the compound is of Formula (I-a-II):

Embodiment 4. The compound of any one of embodiments 0-3, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein the compound is of Formula (I-a-III),

Embodiment 5. The compound of any one of embodiments 1-4, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein R^c and R^d are joined together to form an optionally substituted C_1-6 carbocycle. Embodiment 6. The compound of any one of embodiments 1-5, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein the compound is of Formula (I-a-IV):

Embodiment 7. The compound of any one of embodiments 1-4, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein at least one of R^c and R^d is hydrogen, optionally substituted C1-6 alkyl, halo, or -OH. Embodiment 8. The compound of embodiment 7, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein at each of R^c and R^d is hydrogen and n is 0 or 2. Embodiment 9. The compound of embodiment 7, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein at least one of R^c and R^d is hydrogen and the other is optionally substituted C_1-6 alkyl, halo, or -OH. Embodiment 10. The compound of embodiment 9, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein the compound is of Formula (I-a-V),

wherein R^d is optionally substituted C_1-6 alkyl, halo, or -OH. Embodiment 11. The compound of embodiment 10, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein the compound is of Formula (I-a-VI),

wherein R^d is halo or -OH. Embodiment 12. The compound of any one of embodiments 1-11, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein R^d is fluoro. Embodiment 13. The compound of any one of embodiments 1-11, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein R^d is -OH. Embodiment 14. The compound of any one of embodiments 0-13, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein R^b is optionally substituted alkyl or optionally substituted carbocyclyl. Embodiment 15. The compound of any one of embodiments 0-14, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein R^b is optionally substituted C3-12 carbocyclyl or optionally substituted C_1-6 alkyl. Embodiment 16. The compound of any one of embodiments 0-15, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein R^b is optionally substituted C_3-12 carbocyclyl. Embodiment 17. The compound of any one of embodiments 0-15, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein R^b is of the formula:

wherein: Y is hydrogen, optionally substituted C_1-6 alkyl, halo, or -OR^x; and A is -S- or absent. Embodiment 18. The compound of embodiment 17, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein Y is methyl, ethyl, fluoro, chloro, hydroxyl, or hydrogen. Embodiment 19. The compound of embodiment 1, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein the compound is of Formula (I-b-I):

wherein Y is hydrogen, optionally substituted C1-6 alkyl, halo, or -OR^x. Embodiment 20. The compound of embodiment 19, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein the compound is of Formula (I-b-II):

Embodiment 21. The compound of embodiment 19 or 20, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein the compound is of Formula (I-b-III):

Embodiment 22. The compound of any one of embodiments 19-21, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein the compound is of Formula (I-b-IV):

Embodiment 23. The compound of any one of embodiments 19-22, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein the compound is of Formula (I-b-V):

Embodiment 24. The compound of any one of embodiments 1-23, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein at least one instance of R¹¹ is hydrogen, optionally substituted C_1-6 alkyl, or optionally substituted acyl. Embodiment 25. The compound of any one of embodiments 1-24, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein at least one instance of R¹¹ is hydrogen, methyl, or optionally substituted acyl. Embodiment 26. The compound of any one of embodiments 1-25, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein at least one instance of R¹¹ is methyl. Embodiment 27. The compound of any one of embodiments 1-25, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein at least one instance is R¹¹ is hydrogen. Embodiment 28. The compound of any one of embodiments 1-25, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein each instance of R¹¹ is hydrogen or methyl. Embodiment 29. The compound of any one of embodiments 1-25, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein the optionally substituted acyl is a substituted ester. Embodiment 30. The compound of embodiment 29, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound,

or prodrug thereof, wherein the substituted ester is of the formula , wherein each R^N is independently hydrogen, optionally substituted C_1-6 alkyl, or nitrogen protecting group. Embodiment 31. The compound of embodiment 1, wherein the compound is of the formula:

or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. Embodiment 32. The compound of embodiment 31, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein the compound is:

Embodiment 33. A compound of Formula (II):

. Embodiment 34. The compound of embodiment 33, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein the compound is of Formula (II-a):

Embodiment 35. The compound of embodiment 33, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein the compound is of Formula (II-b):

Embodiment 36. The compound of any one of embodiments 33-35, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein each instance of R^a is independently hydrogen, optionally substituted C1-12 carbocyclyl, optionally substituted C1-6 alkyl, optionally substituted C1-6 heteroalkyl, optionally substituted C6-14 aryl, optionally substituted C5-14 heteroaryl, optionally substituted C_1-8 acyl, or optionally substituted alkyl wherein the alkyl chains are joined, including the nitrogen atom to which they are attached, to form an optionally substituted heterocyclyl. Embodiment 37. The compound of any one of embodiments 33-36, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein at least one instance of R^a is hydrogen, and the second instance of R^a is optionally substituted C_1-12 carbocyclyl, optionally substituted C_1-6 alkyl, optionally substituted C1-6 heteroalkyl, optionally substituted C6-14 aryl, optionally substituted C6- 14 heteroaryl, optionally substituted C1-8 acyl, or optionally substituted alkyl wherein the alkyl chains are joined, including the nitrogen atom to which they are attached, to form an optionally substituted heterocyclyl. Embodiment 38. The compound of any one of embodiments 33-37, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein one instance of R^a is hydrogen, and the second instance of R^a is unsubstituted adamantyl, optionally substituted C1-6 alkyl, optionally substituted C_1-6 heteroalkyl, optionally substituted C₆ aryl, optionally substituted C₆ heteroaryl, optionally substituted C1-8 acyl, or optionally substituted alkyl wherein the alkyl chains are joined, including the nitrogen atom to which they are attached, to form an optionally substituted heterocyclyl. Embodiment 39. The compound of embodiment 38, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof wherein at least one instance of R^a is optionally substituted C_1-6 alkyl. Embodiment 40. The compound of embodiment 39, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein the optionally substituted C1-6 alkyl is substituted with at least one halogen. Embodiment 41. The compound of embodiment 40, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein the optionally substituted C_1-6 alkyl is substituted with at least one fluorine. Embodiment 42. The compound of any one of embodiments 33-38, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein the at least one instance of R^a is unsubstituted C₆ aryl. Embodiment 43. The compound of any one of embodiments 33-38, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein at least one instance of R^a is optionally substituted C1-6 heteroalkyl, optionally wherein one or more backbone carbon atoms in the optionally substituted C_1-6 heteroalkyl are independently replaced with –O–, –NR⁵–, =N–, –N=, –S–, –S(=O)–, –S(=O)2–, –C(=O)–, wherein R⁵ is hydrogen or optionally substituted alkyl. Embodiment 44. The compound of any one of embodiments 33-43, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein each R^a is independently of formula:

, wherein: Y is H, CH₃, CH₂CH₃, CH₂F, CHF₂, CF₃, Cl, Br, I, F, or OH; A is -CH2- or -S-; Z is optionally substituted alkyl, optionally substituted amine, optionally substituted carbocyclyl, or optionally substituted aryl; W is hydrogen, optionally substituted alkyl, or optionally substituted heteroalkyl; and m is 0, 1, or 2. Embodiment 45. The compound of embodiment 44, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein one instance of R^a is hydrogen and the other is of the formula: ,

Embodiment 46. The compound of embodiment 45, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein one instance of R^a is hydrogen and the other is of the formula: ,

Embodiment 47. The compound of any one of embodiments 33-38, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein -N(R^a)2 is of the formula:

, wherein Y’ is hydrogen, optionally substituted alkyl, optionally substituted aryl, halo, or hydroxyl. Embodiment 48. The compound of embodiment 47, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein -N(R^a)2 is of the formula:

Embodiment 49. The compound of any one of embodiments 33-48, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein R¹ is hydrogen, optionally substituted C1-6 alkyl, C_1-6 optionally substituted heteroalkyl, C_1-12 optionally substituted carbocyclyl, or C_1-6 optionally substituted aryl. Embodiment 50. The compound of embodiment 49, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein R¹ is optionally substituted C1-6 heteroalkyl, optionally wherein one or more backbone carbon atoms in the optionally substituted C_1-6 heteroalkyl are independently replaced with –O–, –NR⁵–, =N–, –N=, –S–, –S(=O)–, –S(=O)₂–, –C(=O)–, wherein R⁵ is hydrogen or methyl. Embodiment 51. The compound of any one of embodiments 33-49, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein R¹ is hydrogen. Embodiment 52. The compound of any one of embodiments 33-49, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein R¹ is methyl. Embodiment 53. The compound of any one of embodiments 33-52, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein R² is optionally substituted C1-6 alkyl, optionally substituted C1-6 alkenyl, optionally substituted C1-6 alkynyl, optionally substituted C1-6 heteroalkyl, optionally substituted C_1-6 heteroalkenyl, optionally substituted C_1-6 heteroalkynyl, or optionally substituted acyl. Embodiment 54. The compound of embodiment 53, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein R² is optionally substituted C1-6 heteroalkyne or optionally substituted acyl. Embodiment 55. The compound of embodiment 53 or 54, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein R² is of the formula: or , wherein R⁴ is hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted aryl, or optionally substituted heteroaryl. Embodiment 56. The compound of embodiment 55, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein R⁴ is hydrogen, optionally substituted C1-6 alkyl, or optionally substituted C_1-6 heteroalkyl, optionally wherein the optionally substituted C_1-6 heteroalkyl is substituted with at least one halogen. Embodiment 57. The compound of embodiment 55 or 56, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein R⁴ is-H, -CH3, -CH2F, -CHF2, -CF3, or -CH2Cl. Embodiment 58. The compound of any one of embodiments 55-57, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein R² is of the formula

. Embodiment 59. The compound of any one of embodiments 33-58, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein X is hydrogen, hydroxyl, halogen, or optionally substituted C_1-6 heteroalkyl. _{Embodiment 60. The compound of embodiment 59, or a pharmaceutically acceptable salt,} solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein X is hydrogen. Embodiment 61. The compound of any one of embodiments 33-60, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein X is optionally substituted C1-6 heteroalkyl, optionally wherein one or more backbone carbon atoms in the optionally substituted C1-6 alkyl are independently replaced with –O–, –NR⁵–, =N–, –N=, –S–, –S(=O)–, –S(=O)₂–, –C(=O)–, wherein R⁵ is hydrogen or methyl. _{Embodiment 62. The compound of embodiment 33, wherein the compound is of the} formula:

or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. _{Embodiment 63. A pharmaceutical dosage form comprising:} a core comprising a compound of any one of embodiments 1-62, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the inhibitor of the protease in a large intestine and/or small intestine of a subject to whom the pharmaceutical dosage form is administered. Embodiment 64. A pharmaceutical dosage form, comprising: a core comprising an inhibitor of a protease, wherein the inhibitor comprises a gliptin or a pharmaceutically acceptable salt or other form thereof; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the inhibitor of the protease in a large intestine and/or small intestine of a subject to whom the pharmaceutical dosage form is administered. _{Embodiment 65. The pharmaceutical dosage form of embodiment 64, wherein the protease} cleaves GLP-1. _{Embodiment 66. The pharmaceutical dosage form of any one of embodiments 63-65,} wherein the protease cleaves GLP-2. Embodiment 67. The pharmaceutical dosage form of any one of embodiments 63-66, wherein the protease is a serine protease. Embodiment 68. The pharmaceutical dosage form of any one of embodiments 96-67, wherein the protease is a dipeptidyl peptidase-4 (DPP-4). Embodiment 69. The pharmaceutical dosage form of any one of embodiments 63-68, wherein the protease is a bacterial protease. Embodiment 70. The pharmaceutical dosage form of embodiment 69, wherein the bacterial protease comprises a DPP-4 expressed by B. vulgatus and/or B. dorei. Embodiment 71. The pharmaceutical dosage form of any one of embodiments 63-70, wherein the gliptin comprises saxagliptin, sitagliptin, teneligliptin, omarigliptin, and/or vildagliptin. Embodiment 72. The pharmaceutical dosage form of any one of embodiments 63-71, wherein the gliptin comprises a compound of any one of embodiments 1-62. Embodiment 73. The pharmaceutical dosage form of any one of embodiments 63-72, wherein the controlled release coating is configured to release the inhibitor of the protease in the large intestine. Embodiment 74. The pharmaceutical dosage form of embodiment 73, wherein the controlled release coating is configured to release the inhibitor of the protease in the colon. Embodiment 75. The pharmaceutical dosage form of any one of embodiments 63-72, wherein the controlled release coating is configured to release the inhibitor of the protease in the small intestine. Embodiment 76. The pharmaceutical dosage form of any one of embodiments 63-75, wherein the controlled release coating comprises one or more pH-sensitive materials. Embodiment 77. The pharmaceutical dosage form of any one of embodiments 63-76, wherein the controlled release coating comprises one or more microbe-sensitive materials. Embodiment 78. The pharmaceutical dosage form of any one of embodiments 63-77, wherein the core comprises an amount of the inhibitor sufficient to alleviate one or more symptoms of dysfunctional glucose metabolism and/or regulation. Embodiment 79. The pharmaceutical dosage form of embodiment 78, wherein the one or more symptoms of dysfunctional glucose metabolism and/or regulation comprise dysglycemia. Embodiment 80. The pharmaceutical dosage form of embodiment 78, wherein the one or more symptoms of dysfunctional glucose metabolism and/or regulation comprise excess body fat. Embodiment 81. The pharmaceutical dosage form of any one of embodiments 63-80, wherein the core comprises an amount of the inhibitor sufficient to restore normal glucose metabolism and/or regulation in the subject. Embodiment 82. The pharmaceutical dosage form of any one of embodiments 63-81, wherein the core is in tablet, gelcap, or capsule form. Embodiment 83. A method of treating one or more symptoms of dysfunctional glucose metabolism and/or regulation, comprising: delivering a therapeutically effective amount of an inhibitor of a protease to a large intestine and/or small intestine of a subject, wherein the inhibitor comprises a gliptin or a pharmaceutically acceptable salt or other form thereof. Embodiment 84. The method of embodiment 83, wherein the one or more symptoms of dysfunctional glucose metabolism and/or regulation comprise dysglycemia. Embodiment 85. The method of embodiment 83, wherein the one or more symptoms of dysfunctional glucose metabolism and/or regulation comprise excess body fat. Embodiment 86. The method of any one of embodiments 83-85, wherein the protease cleaves GLP-1. Embodiment 87. The method of any one of embodiments 83-86, wherein the protease cleaves GLP-2. Embodiment 88. The method of any one of embodiments 83-87, wherein the protease is a serine protease. Embodiment 89. The method of any one of embodiments 83-88, wherein the protease is a dipeptidyl peptidase-4 (DPP-4). Embodiment 90. The method of any one of embodiments 83-89, wherein the protease is a bacterial protease. Embodiment 91. The method of embodiment 90, wherein the bacterial protease comprises a DPP-4 expressed by B. vulgatus and/or B. dorei. Embodiment 92. The method of any one of embodiments 83-91, wherein the gliptin comprises saxagliptin, sitagliptin, teneligliptin, omarigliptin, and/or vildagliptin. Embodiment 93. The method of any one of embodiments 83-91, wherein the gliptin comprises a compound of any one of embodiments 1-56. Embodiment 94. The method of any one of embodiments 83-93, wherein delivering the therapeutically effective amount of the inhibitor comprises orally administering a pharmaceutical composition comprising the inhibitor. Embodiment 95. The method of embodiment 94, wherein the pharmaceutical composition comprises: a core comprising the therapeutically effective amount of the inhibitor; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the inhibitor of the bacterial protease in the large intestine and/or small intestine of the subject. Embodiment 96. The method of embodiment 95, wherein the controlled release coating comprises one or more pH-sensitive materials. Embodiment 97. The method of any one of embodiments 95-96, wherein the controlled release coating comprises one or more microbe-sensitive materials. Embodiment 98. The method of any one of embodiments 95-97, wherein the core is in tablet, gelcap, or capsule form. Embodiment 99. The method of any one of embodiments 83-98, wherein delivering the therapeutically effective amount of the inhibitor comprises rectally administering a pharmaceutical composition comprising the inhibitor. Embodiment 100. The method of any one of embodiments 83-99, wherein delivering the therapeutically effective amount of the inhibitor comprises intraperitoneally injecting a pharmaceutical composition comprising the inhibitor. Embodiment 101. The method of any one of embodiments 83-100, wherein the subject is a human subject. Embodiment 102. The method of any one of embodiments83-101, wherein delivering the therapeutically effective amount of the inhibitor of the protease to the large intestine and/or small intestine of the subject comprises delivering the therapeutically effective amount of the inhibitor of the protease to the large intestine of the subject. Embodiment 103. The method of embodiment 102, wherein delivering the therapeutically effective amount of the inhibitor of the protease to the large intestine of the subject comprises delivering the therapeutically effective amount of the inhibitor of the protease to the colon of the subject. Embodiment 104. The method of any one of embodiments -83-101, wherein delivering the therapeutically effective amount of the inhibitor of the protease to the large intestine and/or small intestine of the subject comprises delivering the therapeutically effective amount of the inhibitor of the protease to the small intestine of the subject. Embodiment 105. The method of any one of embodiments 71-104, wherein the therapeutically effective amount is an amount sufficient to alleviate one or more symptoms of glucose metabolism and/or regulation dysfunction. Embodiment 106. The method of embodiment 93, wherein the one or more symptoms of dysfunctional glucose metabolism and/or regulation comprise dysglycemia. Embodiment 107. The method of embodiment 93, wherein the one or more symptoms of dysfunctional glucose metabolism and/or regulation comprise excess body fat. Embodiment 108. A method of treating one or more symptoms of dysfunctional glucose metabolism and/or regulation, comprising: determining an abundance of a bacterial protease in a sample obtained from a subject; and delivering a therapeutically effective amount of an inhibitor of the bacterial protease to a large intestine and/or small intestine of the subject, wherein the inhibitor comprises a gliptin or a pharmaceutically acceptable salt or other form thereof. Embodiment 109. The method of embodiment 108, wherein the one or more symptoms of dysfunctional glucose metabolism and/or regulation comprise dysglycemia. Embodiment 110. The method of embodiment 108, wherein the one or more symptoms of dysfunctional glucose metabolism and/or regulation comprise excess body fat. Embodiment 111. The method of any one of embodiments 108-111, wherein the sample is a fecal sample. Embodiment 112. The method of any one of embodiments 108-111, wherein the bacterial protease cleaves GLP-1. Embodiment 113. The method of any one of embodiments 108-111, wherein the bacterial protease cleaves GLP-2. Embodiment 114. The method of any one of embodiments 108-113, wherein the bacterial protease is a bacterial serine protease. Embodiment 115. The method of any one of embodiments 108-114, wherein the bacterial protease is a bacterial dipeptidyl peptidase-4 (DPP-4). Embodiment 116. The method of embodiment 115, wherein the bacterial DPP-4 comprises a DPP-4 expressed by B. vulgatus and/or B. dorei. Embodiment 117. The method of any one of embodiments 108-116, wherein the gliptin comprises saxagliptin, sitagliptin, teneligliptin, omarigliptin, and/or vildagliptin. Embodiment 118. The method of any one of embodiments 108-117, wherein the gliptin comprises a compound of any one of embodiments 1-55. Embodiment 119. The method of any one of embodiments 108-118, wherein delivering the therapeutically effective amount of the inhibitor of the bacterial protease to the large intestine and/or small intestine of the subject comprises delivering the therapeutically effective amount of the inhibitor of the bacterial protease to the large intestine of the subject. Embodiment 120. The method of embodiment 119, wherein delivering the therapeutically effective amount of the inhibitor of the bacterial protease to the large intestine of the subject comprises delivering the therapeutically effective amount of the inhibitor of the bacterial protease to the colon of the subject. Embodiment 121. The method of any one of embodiments-101-118, wherein delivering the therapeutically effective amount of the inhibitor of the bacterial protease to the large intestine and/or small intestine of the subject comprises delivering the therapeutically effective amount of the inhibitor of the bacterial protease to the small intestine of the subject. Embodiment 122. The method of any one of embodiments 108-121, wherein the therapeutically effective amount is an amount sufficient to alleviate one or more symptoms of glucose metabolism and/or regulation dysfunction. Embodiment 123. The method of embodiment 122, wherein the one or more symptoms of dysfunctional glucose metabolism and/or regulation comprise dysglycemia. Embodiment 124. The method of embodiment 122, wherein the one or more symptoms of dysfunctional glucose metabolism and/or regulation comprise excess body fat. Embodiment 125. A kit comprising: a compound of any one of embodiments 1-62, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, or a pharmaceutical dosing form of one of embodiments 63-82; and instructions for using the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, or the pharmaceutical composition. Embodiment 125. A method comprising administering a protease inhibitor to a subject having one or more signs or symptoms of dysfunctional glucose metabolism and/or regulation. Embodiment 126. A method comprising administering to a subject a compound of any one of embodiments 1-55, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co- crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, or a pharmaceutical dosing form of one of embodiments 63-82. Embodiment 127. The method of embodiment 126, wherein the subject has one or more signs or symptoms of glucose metabolism and/or regulation dysfunction. Embodiment 128. The method of embodiment 127, wherein the one or more signs symptoms of dysfunctional glucose metabolism and/or regulation comprise dysglycemia. Embodiment 129. The method of embodiment 127, wherein the one or more symptoms of dysfunctional glucose metabolism and/or regulation comprise excess body fat. Embodiment 130. The method of embodiment any one of embodiments 126-129, wherein the compound is administered in a therapeutically effective amount. Embodiment 131. The method of embodiment 130, wherein therapeutically effective amount is an amount sufficient to alleviate one or more symptoms of glucose metabolism and/or regulation dysfunction. Embodiment 132. The method of embodiment 126, wherein the compound is administered in an effective amount to induce weight loss in the subject. Embodiment 133. A composition for use in a method of treating dysfunctional glucose metabolism and/or regulation in a subject, the composition comprising a protease inhibitor. Embodiment 134. The composition of embodiment 133, wherein the protease inhibitor comprises a compound of any one of embodiments 1-55, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. Embodiment 135. The composition of embodiment 134, wherein the protease inhibitor comprises a gliptin. Embodiment 136. The composition of embodiment 135, wherein the gliptin comprises saxagliptin, sitagliptin, teneligliptin, omarigliptin, and/or vildagliptin. Embodiment 137. The composition of any one of embodiments 133 to 136, wherein the method comprises delivering an effective amount of the protease inhibitor to a large intestine and/or small intestine of the subject. Embodiment 138. The composition of embodiment 137, wherein the effective amount comprises a therapeutically effective amount. Embodiment 139. The composition of embodiment 137 or 138, wherein the effective amount comprises a prophylactically effective amount. EQUIVALENTS While several embodiments of the present invention have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and/or structures for performing the functions and/or obtaining the results and/or one or more of the advantages described herein, and each of such variations and/or modifications is deemed to be within the scope of the present invention. For example, the skilled artisan will understand that methods of administering compositions described herein also contemplate compositions for use in said methods and for the manufacture of medicaments. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the teachings of the present invention is/are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, the invention may be practiced otherwise than as specifically described and claimed. The present invention is directed to each individual feature, system, article, material, and/or method described herein. In addition, any combination of two or more such features, systems, articles, materials, and/or methods, if such features, systems, articles, materials, and/or methods are not mutually inconsistent, is included within the scope of the present invention. The indefinite articles “a” and “an,” as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to mean “at least one.” The phrase “and/or,” as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Other elements may optionally be present other than the elements specifically identified by the “and/or” clause, whether related or unrelated to those elements specifically identified unless clearly indicated to the contrary. Thus, as a non-limiting example, a reference to “A and/or B,” when used in conjunction with open-ended language such as “comprising” can refer, in one embodiment, to A without B (optionally including elements other than B); in another embodiment, to B without A (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc. As used herein in the specification and in the claims, “or” should be understood to have the same meaning as “and/or” as defined above. For example, when separating items in a list, “or” or “and/or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of” or “exactly one of,” or, when used in the claims, “consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e., “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.” “Consisting essentially of,” when used in the claims, shall have its ordinary meaning as used in the field of patent law. As used herein in the specification and in the claims, the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified ^{within the list of elements to which the phrase “at least one” refers, whether related or unrelated} to those elements specifically identified. Thus, as a non-limiting example, “at least one of A and B” (or, equivalently, “at least one of A or B,” or, equivalently “at least one of A and/or B”) can refer, in one embodiment, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc. Some embodiments may be embodied as a method, of which various examples have been described. The acts performed as part of the methods may be ordered in any suitable way. Accordingly, embodiments may be constructed in which acts are performed in an order different than illustrated, which may include different (e.g., more or less) acts than those that are described, and/or that may involve performing some acts simultaneously, even though the acts are shown as being performed sequentially in the embodiments specifically described above. Use of ordinal terms such as “first,” “second,” “third,” etc., in the claims to modify a claim element does not by itself connote any priority, precedence, or order of one claim element over another or the temporal order in which acts of a method are performed, but are used merely as labels to distinguish one claim element having a certain name from another element having a same name (but for use of the ordinal term) to distinguish the claim elements. In the claims, as well as in the specification above, all transitional phrases such as “comprising,” “including,” “carrying,” “having,” “containing,” “involving,” “holding,” and the like are to be understood to be open-ended, i.e., to mean including but not limited to. Only the transitional phrases “consisting of” and “consisting essentially of” shall be closed or semi-closed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03. EXAMPLES Example 1: Selection of Therapeutic Targets from Bacteroides In this Example, dipeptidyl peptidase-4 (“DPP-4”) from B. vulgatus was selected as a therapeutic target. A pangenomic comparison of S09 family proteases among Bacteroides was performed. Genes from reference genomes of Bacteroides species were aligned to the MEROPS database of proteases. Genes falling under the S09 family of proteases were counted and compared among each reference genome and split by sub-class. It was found the S09.13 proteases were enriched within B. vulgatus and B. dorei organisms. A pangenomic comparison of Bacteroides S09 B/C family proteases and Porphyromonas gingivalis DPP-4 was then performed, with the phylogenetic distance between each sequence falling under the S09 classification being calculated. The S09.65 protease was found to be unique to B. vulgatus and B. dorei. It was also found that the S09.13 proteases were closely related (e.g., had the highest sequence similarity) to human and P. gingivalis DPP-4. Several proteases have been identified as potential therapeutic targets based on the pangenomic comparisons, such as DPP-4 from B. vulgatus, comprising the amino acid sequence set forth in SEQ ID NO: 1: MTKKNLFTLVLCLFCFGTTTHAQRIPTLEEAVYGGLIKTEGGSNVNWMKDGERYSKIEK NAEGAYEVTAYKAKDNSKEVLIPANMLLNPQTGKPISVRNFVFSEDNSKVLIYTNTRRV WRYDTRGDYWVLNLKDGKLQQLGKSLPEATLMFAKFSPDASRVAYVSRNNIYVESLVDG KINQLTQDGNNEIVNGTFDWVYEEEFNCRDGFRWSPDGQYIAYWQSDTQGTGWFDIINN VDSIYPKIQRFPYPKAGTANSAVKVGYVSADGGNTTWLALPGDARNHYIPRMEFIPGCN ELFIQQMNRAQNTNKVWIAKIGENTPVNIFTDQDAAWLETNDNVRWLKGNKYFTWESER DGWRHLYRVSRDGKEIKPITQGAFDYIQEVGADMDKGFVYFIASPDNFTQRYLYRARLF GNGEVKRLSPVDQSGQHRYIMSPSGKWAVHTFSNSETPPVIDMVSFPAHKSIRLITDNA KAKEQYKALGLQPKEFVKTRSGELELDAWMIKPVNFDPSKKYPVIIDVYGEPANATVQD VWSGGSLWHQYLANLGYIIVSIENRGANAPRGREWRKCIYGEVGTFASEDQARGIQDLA RQYSFIDTARIGITGWSGGGSQTLNSMFRYPDVFHTGIAIAFVADQRLYDTVYQERYMN TPQNNPEGYRKGSPISYAAGLKGNLLLIHGTGDDNVHYQNCEMLVNELVRHGKIFSQIS YPMRSHGIYEGEGTSLHLRKTMADYWLKNLPAGGK (SEQ ID NO: 1). Additional non-limiting examples of potential therapeutic targets from B. vulgatus and B. thetaiotaomicron (also referred to as B. theta) which are highly homologous to human DPP-4 are provided in Table E1 below:

Example 2: Inhibition of DPP-4 by Gliptin Compounds In this Example, it was demonstrated that certain gliptins inhibited DPP-4 from B. vulgatus. A standard protease inhibition assay was used. Briefly, recombinant DPP4 enzyme was purified from an overproducing E. coli. 100-200 ng of the purified protein was incubated with 1 mM of chromogenic substrate, Gly-Pro-p-nitroanilide, in PBS, pH 7.4 for 45 minutes at 37°C. Test compounds were added at a starting concentration of 10 mM and serially diluted. The change in absorbance at 405 nm was kinetically measured every 10 minutes and the endpoint data was used to calculate the IC50 values for the enzymes. The effect of six gliptin compounds – sitagliptin, linagliptin, teneligliptin, trelagliptin, omarigliptin, and vildagliptin – on B. vulgatus DPP-4 activity in vitro was evaluated. FIG. 3 shows a plot of percent inhibition as a function of gliptin concentration (µM). It was found that sitagliptin, omarigliptin, teneligliptin, and vildagliptin inhibited B. vulgatus DPP-4 activity in the micromolar range. The IC50 for sitagliptin was 3.17 µM. In contrast, trelagliptin and linagliptin were not found to inhibit B. vulgatus DPP-4 activity. The structures of sitagliptin, omarigliptin, teneligliptin, and vildagliptin are shown in FIG. 2. Select novel compounds show inhibition of human DPP4 with IC50 = 0.00409 µM (cpd 34) and .00343 µM (cpd 49), as well as similar inhibitory activities against a B. thetaiotaomicron DPP4 of IC50 = 0.0032 µM (cpd 34) and 0.00920 µM (cpd 49). Example 3: Synthesis of Certain Compounds In this Example, synthesis of the compounds of the present disclosure are described. Synthesis of a (2S,4S)-1-((S)-2-((3S,5S,7S)-adamantan-1-yl)-2-aminoacetyl)-4-

Step 1: Synthesis of a tert-butyl ((S)-1-((3S,5S,7S)-adamantan-1-yl)-2-((2S,4S)-2-cyano-4- fluoropyrrolidin-1-yl)-2-oxoethyl)carbamate [3a]:

To a stirred solution of (2S,4S)-4-fluoropyrrolidine-2-carbonitrile (2a, 60 mg, 0.4 mmol) in DMF (1 mL, 12.9 mmol) were added (S)-2-((3S,5S,7S)-adamantan-1-yl)-2-((tert- butoxycarbonyl)amino)acetic acid (1a, 90.00 mg, 0.29 mmol), DIPEA (0.1 mL, 0.6 mmol) to the reaction mixture at 0 °C for 5 min. HATU (150 mg, 0.39 mmol) was then added to the reaction mixture at 0 °C and stirred at room temperature for 16 h. Progress of the reaction mass was monitored by TLC and LCMS. Reaction mixture was quenched with ice water and precipitated solid was filtered, washed with water and dried under vacuum to afford tert-butyl ((S)-1- ((3S,5S,7S)-adamantan-1-yl)-2-((2S,4S)-2-cyano-4-fluoropyrrolidin-1-yl)-2-oxoethyl)carbamate (3a, 120 mg, 74% Yield) as a brown solid. LCMS [Column: XBridge BEH C18 (2.1×30)mm, 2.5um, Mobile Phase A: 0.05% TFA in Water, Mobile Phase B: 0.05% TFA in Acetonitrile]: 350.52 [M+H-56]⁺. Step 2: Synthesis of a (2S,4S)-1-((S)-2-((3S,5S,7S)-adamantan-1-yl)-2-aminoacetyl)-4- fluoropyrrolidine-2-carbonitrile [34]:

Tert-butyl ((S)-1-((3S,5S,7S)-adamantan-1-yl)-2-((2S,4S)-2-cyano-4-fluoropyrrolidin-1-yl)-2- oxoethyl)carbamate (3a, 50 mg, 0.12 mmol) was added to a solution of in formic acid (0.4 mL) and water (0.1 mL) at 0 °C. The mixture was slowly allowed to room temperature and stirred for 6 h. Progress of the reaction was monitored by TLC and LCMS. Reaction mixture was evaporated under vacuum. The crude solid was washed with diethyl ether to afford (2S,4S)-1- ((S)-2-((3S,5S,7S)-adamantan-1-yl)-2-aminoacetyl)-4-fluoropyrrolidine-2-carbonitrile (34, 35.6 mg, 95% Yield) as formate salt as an off white solid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 8.18 (s, 1H), 5.39 - 5.54 (m, 1H), 4.93 - 5.02 (m, 1H), 3.91 - 4.03 (m, 1H), 3.72 - 3.86 (m, 1H), 3.02 (s, 1H), 2.43 - 2.47 (m, 2H), 2.30 - 2.38 (m, 1 H), 1.90 - 1.97 (m, 3H), 1.79 (d, J = 11.51 Hz, 3H), 1.62 - 1.69 (m, 3H), 1.54 - 1.62 (m, 3H), 1.46 (d, J = 11.51 Hz, 3H). LCMS [Column: CORTECS UPLC C18 (3.0×30)mm, 1.6um, Mobile Phase A: 0.05% TFA in Water, Mobile Phase B: 0.05% TFA in Acetonitrile]: 306.49 [M+H]⁺. Synthetic experimental write-up for (2S,4S)-1-((S)-2-amino-2-((1s,3R,5R,7S)-3- ethyladamantan-1-yl)acetyl)-4-fluoropyrrolidine-2-carbonitrile [57]:

Step1: Synthesis of methyl (S)-2-((tert-butoxycarbonyl)amino)-2-(-3-fluoroadamantan-1- yl)acetate [2b]:

To a stirred solution of methyl (S)-2-((tert-butoxycarbonyl)amino)-2-(3-hydroxyadamantan-1- yl)acetate (1b, 2 g, 5.89 mmol) in dichloromethane (30 mL) was slowly added diethylaminosulfur trifluoride (1.2 g, 7.07 mmol) in dichloromethane (10 mL) at -78°C. Then, the mixture was stirred for 2 h at room temperature and progress of the reaction was monitored by TLC (20% EtOAc in Heptane, Ninhydrin charring) and LCMS. After completion of the reaction, the mixture quenched with water (30 mL) and extracted with dichloromethane (2 x 50 mL). Combined organic layer was washed with brine (20 mL), dried over Na2SO4 and concentrated under reduced pressure which was further purified by silica gel column chromatography by eluting with 10-12% EtOAc in Heptane to afford methyl (2S)-2-(tert- butoxycarbonylamino)-2-(3-fluoro-1-adamantyl)acetate (1.30 g, 3.77 mmol, 64% Yield) as colourless liquid. LCMS (ESI) m/z [M+H]⁺: 99.6%, tR = 2.51 min; Calculated for C18H28FNO4: 342.20 [M+H]⁺); found 286.56 [M-56+H]⁺; Method Details: TFA BEH 4.2 MINS, Column : Acquity UPLC BEH C18 (2.1*50)mm, 1.7um, Flow rate: 0.5 mL/min. Mobile Phase A: 0.05%TFA in Water, Mobile Phase B: 0.05%TFA in Acetonitrile, Column Temp.: 40°C, Gradient Program Time/B: 0.0/2, 0.3/2,2/98, 3.5/98, 3.6/2,4.2/2. Step-2: methyl (S)-2-((tert-butoxycarbonyl)amino)-2-(3-ethyladamantan-1-yl)acetate [3b]:

To a stirred solution of 2b (500 mg, 1.465 mmol) in dichloromethane (10 mL) was added triethyl aluminium in toluene (5.86 mL, 15 mass%) at 0 °C and the mixture was stirred at room temperature for 6 h. The progress of reaction was monitored by TLC (30% EtOAc in Heptane). After completion of reaction, the mixture was quenched with water (20 mL) and extracted with dichloromethane (2 x 30 mL). Combined organic layer was washed with brine (20 mL), dried over Na2SO4 and concentrated under reduced pressure which was further purified by silica gel column chromatography by eluting with 15% EtOAc in Heptane to afford methyl (S)-2-((tert- butoxycarbonyl)amino)-2-(3-ethyladamantan-1-yl)acetate (200 mg, 0.57 mmol, 39% Yield) as light-yellow semi solid. LCMS (ESI) m/z [M+H]⁺: 99.7%, tR = 2.86 min; Calculated for C₂₀H₃₃NO₄: 352.24[M+H]⁺; found: 296.53 [M-56+H]⁺; Method Details: TFA BEH 4.2 MINS, Column : Acquity UPLC BEH C18 (2.1*50)mm, 1.7um, Flow rate: 0.5 mL/min. Mobile Phase A: 0.05%TFA in Water, Mobile Phase B: 0.05%TFA in Acetonitrile, Column Temp.: 40°C, Gradient Program Time/B: 0.0/2, 0.3/2,2/98, 3.5/98, 3.6/2,4.2/2. Step-3: (S)-2-((tert-butoxycarbonyl)amino)-2-(3-ethyladamantan-1-yl)acetic acid [4b]:

To a stirred solution of 3b (100 mg, 0.28 mmol) in tetrahydrofuran (1 mL), Water (1 mL) and methanol (1 mL) was added lithium hydroxide (40 mg, 1.63 mmol) at room temperature and the resulting mixture was stirred at 60 °C for 3 h. The progress of reaction was monitored by LCMS. After completion of reaction, the mixture was concentrated under reduced pressure to obtain the crude. Then, the crude was acidified using aqueous Citric acid solution (1 mL, 10%), precipitated solid was filtered, washed with cold water (2 mL) and dried to afford (2S)-2-(tert- butoxycarbonylamino)-2-(3-ethyl-1-adamantyl)acetic acid (73 mg, 0.16 mmol, 57% Yield) as white solid. LCMS (ESI) m/z [M+H]⁺:

= 2.63 min; Calculated. for: Chemical Formula: C₁₉H₃₁NO₄: 337.23; found: 282.52 [M-56+H]⁺; Method Details: TFA BEH 4.2 MINS Column : Acquity UPLC BEH C18 (2.1*50)mm, 1.7umFlow rate: 0.5 mL/min. Mobile Phase A: 0.05%TFA in Water, Mobile Phase B: 0.05% TFA in Acetonitrile, Column Temp.: 40°C, Gradient Program Time/B: 0.0/2, 0.3/2,2/98, 3.5/98, 3.6/2,4.2/2. Step-4: tert-butyl ((S)-2-((2S,4S)-2-cyano-4-fluoropyrrolidin-1-yl)-1-(-3-ethyladamantan-1- yl)-2-oxoethyl)carbamate (6b):

To a stirred solution of 4b (85 mg, 0.25 mmol) in DMF (1 mL) were added N,N- diisopropylethylamine (0.09 mL, 0.5 mmol) and HATU (116.00 mg, 0.29592 mmol, 97 mass%) at room temperature. Then, the mixture was stirred for 5 min and 5b (50 mg, 0.33 mmol) was added. Resulting mixture was stirred at room temperature for 6 h and progress of the reaction was monitored by LCMS. After completion of reaction, the mixture was diluted with ice cold water (5 mL) and precipitated solid was filtered, washed with acetonitrile ( 1mL) followed by diethyl ether (2 mL) and dried to afford 6b, tert-butyl ((S)-2-((2S,4S)-2-cyano-4- fluoropyrrolidin-1-yl)-1-(-3-ethyladamantan-1-yl)-2-oxoethyl)carbamate (35 mg, 0.08 mmol, 32% Yield) as white solid. LCMS (ESI) m/z [M+H]⁺: 98.01%, tR = 2.65 min; Calculated for: C₂₄H₃₆FN₃O₃: 434.27; found: 378.60 [M-56+H]⁺; Method Details: TFA BEH 4.2 MIN, Column : Acquity UPLC BEH C18 (2.1*50)mm, 1.7um, Flow rate: 0.5 mL/min. Mobile Phase A: 0.05% TFA in Water, Mobile Phase B: 0.05% TFA in Acetonitrile, Column Temp.: 40°C, Gradient Program Time/B%:0.0/2, 0.3/2,2/98, 3.5/98, 3.6/2,4.2. Step-5: (2S,4S)-1-((S)-2-amino-2-(3-ethyladamantan-1-yl)acetyl)-4-fluoropyrrolidine-2- carbonitrile [57]

To a stirred solution of 6b (35 mg, 0.08072 mmol) in water (0.1 mL) was added formic acid (0.3 mL) at 0 °C and reaction was slowly allowed to room temperature and stirred for 6 h. Progress of the reaction was monitored by TLC. After completion of reaction, the mixture was concentrated under vacuum and obtained crude was triturated with diethyl ether (1 mL). Precipitated solid was filtered and washed with n-heptane and it was stirred for 30 min. Then filtered to afford 57 as a formate salt, (2S,4S)-1-((S)-2-amino-2-(3-ethyladamantan-1-yl)acetyl)- 4-fluoropyrrolidine-2-carbonitrile (26 mg, 0.07798 mmol, 96% Yield) as off white solid. ¹H NMR: (400 MHz, DMSO-d6): δ 8.19 (s, 1H), 5.55 - 5.40 (m, 1H), 5.00 - 4.96 (m, 1H), 4.03 - 3.93 (m, 1H), 3.87 - 3.73 (m, 1H), 3.05 (s, 1H), 2.46 (br d, J = 6.0 Hz, 2H), 1.99 (br s, 2H), 1.79 - 1.64 (m, 3H), 1.53 (br s, 2H), 1.50 - 1.43 (m, 2H), 1.42 - 1.29 (m, 6H), 1.18 (br d, J = 12.0 Hz, 1H), 1.08 (q, J = 7.5 Hz, 2H), 0.76 (t, J = 7.6 Hz, 3H). LCMS (ESI) m/z [M+H]⁺: 96.98%, tR = 2.01 min; Calculated for: C₁₉H₂₈FN₃O: 334.22[M+H]⁺;); found: 334.59 [M+H]⁺; Method Details: TFA BEH 2.5 MIN, Column : Acquity UPLC BEH C18 (2.1*50)mm, 1.7um, Flow rate: 0.5 mL/min. Mobile Phase A: 0.05% TFA in Water, Mobile Phase B: 0.05% TFA in Acetonitrile, Column Temp.: 40°C, Gradient Program Time/B%:0.0/2, 0.3/2,2/98, 3.5/98, 3.6/2,4.2. HPLC: 78%, = 8.348 min; Column: X-Select C18 (4.6x150) mm 3.5µm, Mobile Phase: A - 5mM Ammonium Bicarbonate in water, Mobile Phase B: Acetonitrile (100 %), Flow Rate: 1.0 mL/ min, Gradient: Time(min)/B Conc. : 0.01/5, 1.0/5, 8.0/100, 12.0/100, 14.0/5, 18.0/5 Step-5: (2S,4S)-1-((S)-2-amino-2-(3-ethyladamantan-1-yl)acetyl)-4-fluoropyrrolidine-2- carbonitrile [57]

To a stirred solution of 6b (35 mg, 0.08072 mmol) in water (0.1 mL) was added formic acid (0.3 mL) at 0 °C and reaction was slowly allowed to room temperature and stirred for 6 h. Progress of the reaction was monitored by TLC. After completion of reaction, the mixture was concentrated under vacuum and obtained crude was triturated with diethyl ether (1 mL). Precipitated solid was filtered and washed with n-heptane and it was stirred for 30 min. Then filtered to afford 57 as a formate salt, (2S,4S)-1-((S)-2-amino-2-(3-ethyladamantan-1-yl)acetyl)- 4-fluoropyrrolidine-2-carbonitrile (26 mg, 0.07798 mmol, 96% Yield) as off white solid. ¹H NMR: (400 MHz, DMSO-d6): δ 8.19 (s, 1H), 5.55 - 5.40 (m, 1H), 5.00 - 4.96 (m, 1H), 4.03 - 3.93 (m, 1H), 3.87 - 3.73 (m, 1H), 3.05 (s, 1H), 2.46 (br d, J = 6.0 Hz, 2H), 1.99 (br s, 2H), 1.79 - 1.64 (m, 3H), 1.53 (br s, 2H), 1.50 - 1.43 (m, 2H), 1.42 - 1.29 (m, 6H), 1.18 (br d, J = 12.0 Hz, 1H), 1.08 (q, J = 7.5 Hz, 2H), 0.76 (t, J = 7.6 Hz, 3H). LCMS (ESI) m/z [M+H]⁺: 96.98%, tR = 2.01 min; Calculated for: C₁₉H₂₈FN₃O: 334.22[M+H]⁺;); found: 334.59 [M+H]⁺; Method Details: TFA BEH 2.5 MIN, Column : Acquity UPLC BEH C18 (2.1*50)mm, 1.7um, Flow rate: 0.5 mL/min. Mobile Phase A: 0.05% TFA in Water, Mobile Phase B: 0.05% TFA in Acetonitrile, Column Temp.: 40°C, Gradient Program Time/B%:0.0/2, 0.3/2,2/98, 3.5/98, 3.6/2,4.2. HPLC: = 8.348 min; Column: X-Select C18 (4.6x150) mm 3.5µm, Mobile Phase: A - 5mM Ammonium Bicarbonate in water, Mobile Phase B: Acetonitrile (100 %), Flow Rate: 1.0 mL/ min, Gradient: Time(min)/B Conc. : 0.01/5, 1.0/5, 8.0/100, 12.0/100, 14.0/5, 18.0/5 Example 4: Mass Spectrum and IC50 Analysis of Certain Compounds In this Example, provided is the mass spectrum and IC50 data for disclosed compounds.

Example 5: Effects of Certain Compounds on Diet Induced Obesity (DIO) Mouse Models In this example, effects of certain compounds on blood glucose and liver function in mouse models of diet-induced obesity. Male C57Bl/6J mice, aged 18-20 weeks, were procured from Jackson Laboratory (USA). Mice were fed either normal chow diet or high fat diet (60 kcal%) for 14-16 weeks prior to procurement. Animals were randomized based on body weight and blood glucose levels on Day 1. They were then maintained on either the normal diet (ND) or High Fat diet (HFD) (depending on the experimental groups) throughout the duration of the experiment to induce obesity (e.g., as described by Bagnol, D., et al. (2012). Current Protocols in Neuroscience, 59(1), 9-38.). Animals were administered the test compounds or vehicle (PBS, pH 7.4) once every day for 28 days by oral gavage. Body weight and feed intake were measured every other day. Blood glucose was measured weekly using a glucometer in non-fasted animals. Plasma lipid and other clinical marker analyses (e.g., liver function tests) were performed using the plasma collected at the end of the study on Day 30. As shown in FIGs. 3A-3B, mice receiving HFD and treated with 50mg/kg of compound 34 were resistant to weight gain at levels at least comparable to mice treated with sitagliptin; similarly, measures of food consumption are suggestive of reduced appetite in mice treated with the same compound. Further, as shown in FIGs. 5 and 6, liver enzyme levels and cholesterol markedly improved in mice treated with compound 34. For the oral glucose tolerance test, on Day 28, mice were fasted overnight (10-12 hours). The following morning, the test compound was administered 1 hour before the mice were administered a glucose load of 2 gm/kg. Plasma glucose was measured at different time points using a glucometer. FIGs. 4A-4C demonstrate the beneficial effects of compound 34 on blood glucose after oral glucose tolerance test- as exemplified by FIG. 4B and 4C, blood glucose levels in mice treated with compound 34 were reduced to near-normal, and were at least comparable to blood glucose levels in mice treated with sitagliptin. Example 7: Effects of Certain Compounds on Epithelial Barrier Integrity FIG. 7A shows a plot of trans-epithelial electrical resistance (“TEER”) as a function of time (hours) for T84 intestinal cells. It was found that intestinal cells with DPP-4 from B. vulgatus (labeled “DPP-4”) had significantly lower TEER values than intestinal cells without DPP-4 from B. vulgatus (labeled “Cell control”), indicating an association of B. vulgatus DPP-4 with disruption of epithelial barrier integrity. It was further found that adding a protease inhibitor (1x Roche Complete EDTA-Free Protease Inhibitor Cocktail) to intestinal cells with DPP-4 from B. vulgatus significantly increased TEER values, resulting in TEER values that were relatively close to those of the intestinal cells without DPP-4 from B. vulgatus. FIG. 7 thus demonstrates that DPP-4 from B. vulgatus reduces intestinal barrier integrity and that addition of a protease inhibitor mitigates the effects of DPP-4. Given the effect of Bacteroides DPP-4 on intestinal barrier integrity, bacterial proteases may be related to the development of certain dysfunctions of glucose metabolism and/or regulation. FIG. 7B shows percent adherence and invasion of intestinal cells for wild-type B. vulgatus with DPP-4 (left) and B. vulgatus with DPP-4 genetically removed (right). It was found that removing DPP-4 prevented B. vulgatus from adhering to and invading intestinal cells.

Claims

CLAIMS What is claimed is: 1. A method of treating one or more symptoms of dysfunctional glucose metabolism and/or regulation in a subject, the method comprising delivering a therapeutically effective amount of a protease inhibitor to a gastrointestinal (GI) tract of the subject, thereby treating the one or more symptoms.

2. The method of claim 1, wherein the one or more symptoms of dysfunctional glucose metabolism and/or regulation comprise dysglycemia and/or excess body fat.

3. The method of claim 1, wherein the protease cleaves glucagon-like peptide (GLP) 1 (GLP-1), GLP-2, and/or glucose-dependent insulinotropic peptide (GIP).

4. The method of claim 1, wherein the protease is a serine protease.

5. The method of claim 1, wherein the protease is a dipeptidyl peptidase-4 (DPP-4).

6. The method of claim 1, wherein the protease is a bacterial protease, optionally wherein the bacterial protease comprises a DPP-4 expressed by a species of Bacteroides, further optionally wherein the bacterial protease is expressed by B. vulgatus, B. thetaiotaomicron, and/or B. dorei.

7. The method of claim 1, wherein the protease inhibitor comprises a gliptin, optionally wherein the gliptin comprises saxagliptin, sitagliptin, teneligliptin, omarigliptin, vildagliptin, or a combination thereof.

8. The method of claim 1, wherein the protease inhibitor comprises a compound of Formula (I), a compound of Formula (II), or a pharmaceutically acceptable salt or other form thereof, optionally wherein the compound of Formula (I) is any one of Compound No. 26-57 and the compound of Formula (II) is any one of Compound No. 1-24.

9. The method of claim 1, wherein the composition comprises: a core comprising the effective amount of the protease inhibitor; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the protease inhibitor in the large intestine and/or small intestine of the subject.

10. A method of treating one or more symptoms of dysfunctional glucose metabolism and/or regulation, the method comprising: (i) determining an abundance of a bacterial protease in a sample obtained from a subject; and (ii) delivering a therapeutically effective amount of an inhibitor of the bacterial protease to the gastrointestinal (GI) tract of the subject; optionally: wherein the inhibitor of the bacterial protease comprises a compound of Formula (I), a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof; and/or wherein the inhibitor of the bacterial protease comprises a gliptin or a pharmaceutically acceptable salt or other form thereof, further optionally wherein the gliptin comprises saxagliptin, sitagliptin, teneligliptin, omarigliptin, or vildagliptin.

11. The method of claim 10, wherein the sample is a fecal sample.

12. A method comprising providing an effective amount of a protease inhibitor to a subject having one or more signs or symptoms of dysfunctional glucose metabolism and/or regulation, wherein the protease inhibitor comprises a compound of Formula (I), a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof; optionally wherein the compound of Formula (I) is any one of Compound No. 26-57 and the compound of Formula (II) is any one of Compound No.1-24.

13. The method of claim 12, wherein the providing comprises delivering the effective amount of the protease inhibitor to gastrointestinal (GI) tract of the subject.

14. A pharmaceutical composition for use in a method of treating one or more symptoms of dysfunctional glucose metabolism and/or regulation in a subject, the pharmaceutical composition comprising a therapeutically effective amount of a protease inhibitor, optionally wherein the pharmaceutical composition comprises: a core comprising a protease inhibitor, wherein the protease inhibitor comprises a gliptin or a pharmaceutically acceptable salt or other form thereof; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the protease inhibitor in the gastrointestinal (GI) tract of the subject.

15. A method of treating one or more symptoms of dysfunctional glucose metabolism and/or regulation in a subject, the method comprising reducing the activity of a bacterial protease in a subject, optionally wherein the bacterial protease is a bacterial dipeptidyl peptidase-4 (DPP-4), further optionally wherein the bacterial DPP-4 comprises a DPP-4 expressed by B. vulgatus, B. thetaiotaomicron, and/or B. dorei.