[go: up one dir, main page]

WO2025080777A1 - Fragments peptidiques ad36e4orf1 en tant qu'agents antidiabétiques - Google Patents

Fragments peptidiques ad36e4orf1 en tant qu'agents antidiabétiques Download PDF

Info

Publication number
WO2025080777A1
WO2025080777A1 PCT/US2024/050683 US2024050683W WO2025080777A1 WO 2025080777 A1 WO2025080777 A1 WO 2025080777A1 US 2024050683 W US2024050683 W US 2024050683W WO 2025080777 A1 WO2025080777 A1 WO 2025080777A1
Authority
WO
WIPO (PCT)
Prior art keywords
administration
e4orfl
seq
peptide fragment
composition
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2024/050683
Other languages
English (en)
Inventor
Nikhil V. Dhurandhar
Vijay HEGDE
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Texas Tech University TTU
Texas Tech University System
Original Assignee
Texas Tech University TTU
Texas Tech University System
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Texas Tech University TTU, Texas Tech University System filed Critical Texas Tech University TTU
Publication of WO2025080777A1 publication Critical patent/WO2025080777A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/162—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from virus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/10011—Adenoviridae
    • C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
    • C12N2710/10322—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/10011—Adenoviridae
    • C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
    • C12N2710/10332—Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent

Definitions

  • Numerous embodiments of the present disclosure aim to address the aforementioned need.
  • the present disclosure pertains to a composition that includes at least one early gene 4 open reading frame 1 (E4orfl) peptide fragment.
  • the E4orfl peptide fragment includes, without limitation, REGHPVGTLLLERVIFPSVRIATLV (SEQ ID NO: 1) or a sequence with at least 65% sequence identity to SEQ ID NO: 1 ; YQGRFMALNDYHARGILTQSDVIFAGRRHDLSVLLFNHTDRFLYVREGHPVGTLLLERV IFPSVRIATLV (SEQ ID NO: 2) or a sequence with at least 65% sequence identity to SEQ ID NO: 2; or combinations thereof.
  • the methods of the present disclosure may be utilized to treat or prevent various metabolic disorders in subjects.
  • the metabolic disorders include, without limitation, prediabetes, Type 1 Diabetes (T1D), Type 2 Diabetes (T2D), insulin resistance, hyperinsulinemia, hyperglycemia, metabolic syndrome, hepatic steatosis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steato-hepatitis (NASH), liver dysfunction characterized by fatty liver and/or insulin resistance, polycystic ovary syndrome, or combinations thereof.
  • FIG. 1A illustrates how the early gene 4 open reading frame 1 (E4orfl) bypasses the proximal insulin signaling pathway but activates distal insulin signaling.
  • FIG. IB shows the E4orfl amino acid sequence, with the PDZ domain binding (PBM) motif underlined.
  • FIGS. 2A-2C show nanoparticle transmission electron microscopy (TEM) imaging of void nanoparticles (FIG. 2A), nanoparticles treated with a 25 amino acid E4orfl peptide fragment (FIG. 2B), and nanoparticles treated with E4orfl (FIG. 2C).
  • TEM nanoparticle transmission electron microscopy
  • FIG. 3 shows a Western blot of phospho (p)-Akt ( ⁇ 60 kDa) and total Akt ( ⁇ 60 kDa) expression in 3T3L1 cells treated with void nano-liposomes (Void NP), E4orfl nano-liposomes (E4 NP) and 100 nM insulin (Insulin) for 24 h. Bar graphs show p-Akt levels normalized to total Akt, which is significantly higher in the E4 NP group than void NP groups (ANOVA, P ⁇ 0.05).
  • FIGS. 1 shows a Western blot of phospho (p)-Akt ( ⁇ 60 kDa) and total Akt ( ⁇ 60 kDa) expression in 3T3L1 cells treated with void nano-liposomes (Void NP), E4orfl nano-liposomes (E4 NP) and 100 nM insulin (Insulin) for 24 h. Bar graphs show p-Akt levels normalized to total
  • 4A-4B show Western blots of phospho (p)-Akt ( ⁇ 60 kDa) and total Akt ( ⁇ 60 kDa) expression in 3T3-L1 cells treated with 70 pl of void NP, E4orfl NP, P5 NP, P5L NP, P25 NP and 100 nM insulin (Insulin) for 12 h and 24 hr.
  • Bar graphs show p-Akt levels normalized to total Akt levels, which is not significant in peptide NP treated groups (P5, P5L, P25) compared to void NP treated groups.
  • Akt activation is significantly higher in E4 NP group compared to void NP groups and peptides NP treated group (ANOVA, P ⁇ 0.05).
  • FIGS. 5A-5B show Western blots of phospho (p)-Akt ( ⁇ 60 kDa) and total Akt ( ⁇ 60 kDa) expression in 3T3L1 cells treated with 70 pl of void NP, E4orfl NP, P25 NP and 100 nM insulin (Insulin) for 48 h and 72 hr. Bar graphs show p-Akt levels normalized to total Akt levels, which is not significant in P25 NP treated groups and E4orfl NP compared to void NP treated groups (ANOVA, P ⁇ 0.05).
  • FIGS. 6A-6B show Western blots of phospho (p)-Akt ( ⁇ 60 kDa) and total Akt ( ⁇ 60 kDa) expression in 3T3-L1 cells treated with 70 pl of void NP, P5 NP, and P25 NP for 12 hr.
  • FIG. 6A shows bar graphs of p-Akt levels normalized to total Akt levels, which is significant in the P25 NP treated group when compared to the void NP treated group (ANOVA, P ⁇ 0.05).
  • FIG. 6B shows subsequent experiments, which did not show any significant difference between the P25 NP treated group when compared to Void NP treated group.
  • FIGS. 7A-7B show P25 NP-mediated glucose uptake results.
  • FIG. 7A shows raw data before normalization, which shows a significant difference in the P25 treated group when compared to the Void NP treated group after 12 hours (ANOVA, P ⁇ 0.05).
  • FIG. 7B provides additional data, which shows no significant difference in the P25 NP treated group when compared to the Void NP treated group 12 hours after normalization (ANOVA, P ⁇ 0.05).
  • FIGS. 8A-8B show Western blots of phospho (p)-Akt ( ⁇ 60 kDa) and total Akt ( ⁇ 60 kDa) expression in 3T3-L1 cells treated with 0.208 pM P70 Ad36E4orfl peptide for 12 h and 24 hr. Bar graphs show p-Akt levels normalized to total Akt levels, which is significant in peptide P70- NP treated cells for 12h compared with void NP treated cells. DETAILED DESCRIPTION
  • Insulin resistance is one of the common features of T2D. As illustrated in FIG. 1A, the insulin signaling pathway mainly consists of a metabolic and a mitogen arm. Most metabolic effects of insulin are related to the PI3K/AKT pathway.
  • the pathogeneses due to insulin resistance are mainly connected with the PI3K/AKT pathway.
  • the PI3K/AKT pathway is divided into proximal and distal insulin signaling. Insulin binds to the insulin receptor on the cell membrane followed by autophosphorylation of insulin receptor substrate 1 (IRS1) and insulin receptor substrate 2 (IRS2) that subsequently activates the PI3K/AKT pathway.
  • IRS1 insulin receptor substrate 1
  • IRS2 insulin receptor substrate 2
  • Phosphorylation of the PI3K/AKT pathway activates Akt, leading to glucose transporter 4 (Glut 4) translocation to the cell membrane for glucose uptake.
  • Conformational changes of IRS1 and IRS2 refer to the proximal signaling pathway while the PI3K/AKT and Glut 4 indicate the distal signaling pathway.
  • the proximal signaling pathway becomes incapable of sending signals for cellular uptake of glucose from the blood during insulin resistance status.
  • most of the available anti-diabetic medications such as secretagogues, insulin mimetics, or sensitizers focus on the activation of the proximal insulin signaling for enhancing cellular glucose uptake.
  • Numerous embodiments of the present disclosure aim to address the aforementioned need.
  • the present disclosure pertains to a composition that includes at least one early gene 4 open reading frame 1 (E4orfl) peptide fragment.
  • the E4orfl peptide fragment includes, without limitation, REGHPVGTLLLERVIFPSVRIATLV (SEQ ID NO: 1) or a sequence with at least 65% sequence identity to SEQ ID NO: 1;
  • compositions of the present disclosure can have numerous embodiments.
  • compositions of the present disclosure can include various E4orfl peptide fragments.
  • the E4orf 1 peptide fragment includes a sequence with at least 65% sequence identity to SEQ ID NO: 1.
  • the E4orfl peptide fragment includes a sequence with at least 70% sequence identity to SEQ ID NO: 1.
  • the E4orfl peptide fragment includes a sequence with at least 75% sequence identity to SEQ ID NO: 1 .
  • the E4orf 1 peptide fragment includes a sequence with at least 80% sequence identity to SEQ ID NO: 1.
  • the E4orfl peptide fragment includes a sequence with at least 65% sequence identity to SEQ ID NO: 2. In some embodiments, the E4orfl peptide fragment includes a sequence with at least 70% sequence identity to SEQ ID NO: 2. In some embodiments, the E4orfl peptide fragment includes a sequence with at least 75% sequence identity to SEQ ID NO: 2. In some embodiments, the E4orfl peptide fragment includes a sequence with at least 80% sequence identity to SEQ ID NO: 2. In some embodiments, the E4orfl peptide fragment includes a sequence with at least 85% sequence identity to SEQ ID NO: 2.
  • the E4orfl peptide fragment includes a sequence with at least 90% sequence identity to SEQ ID NO: 2. In some embodiments, the E4orfl peptide fragment includes a sequence with at least 95% sequence identity to SEQ ID NO: 2. In some embodiments, the E4orfl peptide fragment includes a sequence with at least 99% sequence identity to SEQ ID NO: 2. In some embodiments, the E4orfl peptide fragment includes SEQ ID NO: 2.
  • compositions of the present disclosure may be in various forms. For instance, in some embodiments, the compositions of the present disclosure may be in the form of a liquid. In some embodiments, the compositions of the present disclosure may be in the form of a solid. In some embodiments, the compositions of the present disclosure may be in lyophilized form.
  • compositions of the present disclosure pertain to methods of modulating cellular glucose uptake by associating cells with a composition of the present disclosure.
  • the compositions of the present disclosure may be associated with various cells.
  • the cells include fat cells, muscle cells, or liver cells.
  • the compositions of the present disclosure may have various effects on cells.
  • the compositions of the present disclosure increase cellular glucose uptake.
  • the compositions of the present disclosure increase cellular glucose uptake independently of proximal insulin signaling pathways.
  • the compositions of the present disclosure can cause an increase in cellular glucose uptake in fat cells, muscle cells, or liver cells.
  • compositions of the present disclosure may become associated with cells in various manners. For instance, in some embodiments, the association of cells with the compositions of the present disclosure occurs in vitro. In some embodiments, the association of cells with the compositions of the present disclosure occurs in vivo in a subject.
  • Additional embodiments of the present disclosure pertain to methods of treating or preventing a metabolic disorder in a subject by administering a composition of the present disclosure to a subject.
  • the methods of the present disclosure can have numerous embodiments.
  • the methods of the present disclosure may be utilized to treat or prevent various metabolic disorders in subjects.
  • the metabolic disorders include, without limitation, prediabetes, Type 1 Diabetes (T1D), Type 2 Diabetes (T2D), insulin resistance, hyperinsulinemia, hyperglycemia, metabolic syndrome, hepatic steatosis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steato-hepatitis (NASH), liver dysfunction characterized by fatty liver and/or insulin resistance, polycystic ovary syndrome, or combinations thereof.
  • the metabolic disorder includes Type 1 Diabetes (T1D).
  • the metabolic disorder includes Type 2 Diabetes (T2D).
  • compositions of the present disclosure increase cellular glucose uptake in a subject. In some embodiments, the compositions of the present disclosure increase cellular glucose uptake independently of proximal insulin signaling pathways. In some embodiments, the compositions of the present disclosure can cause an increase in cellular’ glucose uptake in fat cells, muscle cells, liver cells, or combinations thereof.
  • compositions of the present disclosure may be administered to subjects in various manners.
  • the administration occurs by a method that includes, without limitation, electroporation, transfection, oral administration, inhalation, subcutaneous administration, intravenous administration, intraperitoneal administration, intramuscular administration, injection, intrathecal injection, intra-articular administration, topical administration, central administration, peripheral administration, aerosol-based administration, nasal administration, intranasal administration, transmucosal administration, transdermal administration, parenteral administration, or combinations thereof.
  • the administration occurs by a method that includes, without limitation, oral administration, intramuscular administration, intranasal administration, subcutaneous administration, transdermal administration, intravenous administration, or combinations thereof.
  • compositions of the present disclosure may be administered to various subjects.
  • the subject is a human being.
  • the subject is a non-human mammal.
  • the non-human mammal includes, without limitation, a horse, a rabbit, a mouse, a rat, a pig, a sheep, a cow, a dog, or a cat.
  • the non-human mammal is a domestic animal, such as a dog or a cat.
  • the subject is suffering from a metabolic disorder.
  • the subject is vulnerable to a metabolic disorder.
  • Applicant identified a 125 amino acid protein encoded by the E4orfl gene (i.e., early gene 4 open reading frame 1) from a human adenovirus (Ad36) that shows anti- hyperglycemic effects in vitro (preadipocytes, adipocytes, myoblast cells, and/or skeletal muscles) and in animal models.
  • This protein (Ad36E4orfl) shows potential in reducing blood glucose levels and increasing cellular glucose uptake, despite insulin resistance, by bypassing the impaired proximal insulin signaling pathway and preferentially activating the distal insulin signaling pathway.
  • Ad36E4orfl the insulin-independent action of Ad36E4orfl makes it a novel and potential drug for both type 1 and type 2 diabetes disorders.
  • this protein shows in vivo and in vitro suppression of glucose output and lipid accumulation in the liver, which indicates the promising role of Ad36E4orfl in preventing progression of hepatic steatosis.
  • Ad36E4orfl protein offers a research opportunity to develop a new anti-diabetic drug with multiple potential advantages.
  • the Ad36E4orfl protein is not naturally expressed in the human body. Therefore, this protein should preferably associate with a delivery system to enter cells and exert its action.
  • Applicant s lab previously established a lipid-based nanoparticle, which shows successful transport and anti-diabetic effects of the E4orfl protein through distal cell signaling pathway in mouse-derived preadipocyte (3T3-L1) cell lines.
  • the purified E4orfl protein contains a Glutathione Sepharose Transferase (GST) tag, which is commonly used for protein purification. Removal of this tag is challenging as it compromises total protein yield.
  • GST Glutathione Sepharose Transferase
  • a tagged protein could elicit an immune response in vivo (e.g., opsonization by serum proteins and clearance by the mononuclear phagocytic system), which is not desirable.
  • Ad36E4orfl protein sequence consists of a PDZ domain binding (PBM) motif, which is required for its function (FIG. IB).
  • PBM PDZ domain binding
  • Previous experiments by Applicant showed that Ad36E4orfl needs the PBM region to exert its function.
  • Applicant designed peptides of varying amino acid lengths containing the PBM sequence.
  • Nanoliposomes are clinically relevant to deliver Ad36E4orfl. Liposomes are among the well-known nanoparticles and liposomal pharmaceutical products that were approved by the US Food and Drug Administration (FDA) in 1995 for the treatment of chemotherapy-refractory acquired immune deficiency syndrome (AIDS)-related Kaposi’s sarcoma. Current applications of liposomes are in immunology, dermatology, vaccine adjuvant, eye disorders, brain targeting, infective disease and in tumor therapy. Liposome-mediated drug delivery systems also inhibit rapid clearance of liposomes by controlling size, charge, and surface hydration. In addition, liposomes protect encapsulated substances from physiological degradation.
  • FDA US Food and Drug Administration
  • AIDS acquired immune deficiency syndrome
  • AIDS acquired immune deficiency syndrome
  • Current applications of liposomes are in immunology, dermatology, vaccine adjuvant, eye disorders, brain targeting, infective disease and in tumor therapy. Liposome-mediated drug delivery systems also inhibit rapid clearance of liposomes by
  • liposomes provide higher therapeutic effects, optimal biocompatibility, and optimal safety. Therefore, in delivering Ad36E4orfl and its peptide fragments, nanoparticlc technology can protect peptides and proteins from degradation, improve the half-life of peptides and proteins, control protein release, and target different tissues in the body.
  • FIGS. 2A-2C show the void nanoparticle (FIG. 2A), nanoparticles treated with peptide-25 (FIG. 2B), and nanoparticles treated with E4orfl protein (FIG. 2C).
  • FIGS. 2A-2C show the void nanoparticle (FIG. 2A), nanoparticles treated with peptide-25 (FIG. 2B), and nanoparticles treated with E4orfl protein (FIG. 2C).
  • FIGS. 2A-2C the spherical shape of the nanoparticles is preserved when encapsulated with the 25aa peptide and the 125aa Ad36E4orfl protein, which is consistent with Applicant’s previous observations.
  • the size of the nanoparticles extracted from the images were in the range of 70-100 nm.
  • TEM imaging confirms the desired morphology and the size distribution of Applicant’s nanoparticles (FIGS. 2A-2C).
  • Applicant next determined a dose dependent effect of P5 and P25 (0.25ug/ul and 0.50ug/ul) on Akt phosphorylation in 3T3-L1 cells.
  • P5 and P25 (0.25ug/ul and 0.50ug/ul)
  • Akt phosphorylation in 3T3-L1 cells.
  • FIGS. 6A-6B nanoliposome encapsulated 0.25ug/ul P25 showed significant Akt phosphorylation following 12h treatment compared with void treated control cells (FIG. 6A).
  • a follow up experiment did not show the previously observed result (FIG. 6B).
  • Example 2 Activation of Insulin signaling by a 70aa Ad36E4orfl peptide
  • Example 1 Applicant reported that the Ad36E4orfl 25aa peptide (P25) could improve cellular glucose uptake by activating the insulin independent distal insulin signaling. To further examine other Ad36E4orfl peptides, Applicant tested the effect of a peptide 70aa in length as shown in Table 2. E4orfl peptide fragment name Sequence (NH2 to COOH)
  • P70 is a 70 amino acid sequence synthetic peptide.
  • the molecular weight of this peptide is 8083.38 Dalton.
  • Murine 3T3-L1 pre-adipocytes were treated with either 0.208 uM P70 Ad36E4orfl peptide encapsulated nanoliposomes (peptide) or void nanoliposomes (void) for 12 or 24 hours (h).
  • P70 Ad36E4orfl peptide encapsulated nanoliposomes peptide
  • void nanoliposomes void
  • FIG. 8A 3T3-L1 cells treated with P70 Ad36E4orfl peptide for 12h significantly increase pAkt protein expression compared with void treated control cells.
  • Cells treated for 24h with P70 Ad36E4orfl peptide did not show any increase in pAkt expression (FIG. 8A).
  • Ad36E4orfl protein expression in these cells Protein lysates from transgenic mice expressing the 125aa Ad36E4orfl protein was used as a positive control. P70 Ad36E4orfl peptide treated cells for 12h show protein expression, which is absent in the void cells, confirming protein translation of the peptide (FIG. 8B).

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Diabetes (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Virology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Immunology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Des modes de réalisation de la présente divulgation concernent une composition qui comprend au moins un fragment peptidique du premier cadre ouvert de lecture du gène précoce 4 (E4orf1). Le fragment peptidique E4orf1 comprend, sans limitation, SEQ ID NO : 1 ou une séquence ayant au moins 65 % d'identité de séquence avec SEQ ID NO : 1, SEQ ID NO : 2 ou une séquence ayant au moins 65 % d'identité de séquence avec SEQ ID NO : 2 ; ou des combinaisons de ceux-ci. Des modes de réalisation supplémentaires de la présente divulgation concernent des procédés de modulation de l'absorption de glucose cellulaire par association de cellules à une composition de la présente divulgation. Certains autres modes de réalisation de la présente divulgation concernent des méthodes de traitement ou de prévention d'un trouble métabolique chez un sujet par l'administration d'une composition de la présente divulgation au sujet.
PCT/US2024/050683 2023-10-10 2024-10-10 Fragments peptidiques ad36e4orf1 en tant qu'agents antidiabétiques Pending WO2025080777A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202363543338P 2023-10-10 2023-10-10
US63/543,338 2023-10-10

Publications (1)

Publication Number Publication Date
WO2025080777A1 true WO2025080777A1 (fr) 2025-04-17

Family

ID=95396369

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2024/050683 Pending WO2025080777A1 (fr) 2023-10-10 2024-10-10 Fragments peptidiques ad36e4orf1 en tant qu'agents antidiabétiques

Country Status (1)

Country Link
WO (1) WO2025080777A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9433659B2 (en) * 2012-01-20 2016-09-06 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
WO2021026495A1 (fr) * 2019-08-07 2021-02-11 Texas Tech University System Traitement thérapeutique de la maladie d'alzheimer à l'aide d'ad36e40rf1

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9433659B2 (en) * 2012-01-20 2016-09-06 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor
WO2021026495A1 (fr) * 2019-08-07 2021-02-11 Texas Tech University System Traitement thérapeutique de la maladie d'alzheimer à l'aide d'ad36e40rf1

Similar Documents

Publication Publication Date Title
US12233109B2 (en) Long-acting GLP-1r agonist as a therapy of neurological and neurodegenerative conditions
US20060084597A2 (en) Use of compounds having gip activity for the treatment of disorders associated with abnormal loss of cells and/or for the treatment of obesity
US20110207673A1 (en) Methods and compositions for modulating drug-polymer architecture, pharmacokinetics and biodistribution
US20230057249A1 (en) Targeted protein contrast agents, methods of making, and uses thereof
JP2013530993A (ja) 治療用コンジュゲートのための短く且つｄ−アミノ酸を含有するポリペプチドおよびその使用
US20250302882A1 (en) Pharmaceutical composition for preventing or treating neurodegenerative disease, containing, as active ingredients, cyclodextrin and stem cells in which vegf is overexpressed
KR20230087495A (ko) 알츠하이머 질환을 치료하기 위한 β-아밀로이드 백신
Zhang et al. Pro-GLP-1, a Pro-drug of GLP-1, is neuroprotective in cerebral ischemia
JP2002502369A (ja) 胃腸管上部の機能を強化する方法
CN107847560A (zh) 包括eno1的组合物以及其在治疗肥胖症或超重和减少体重增加的方法中的用途
WO2025080777A1 (fr) Fragments peptidiques ad36e4orf1 en tant qu'agents antidiabétiques
KR20220007320A (ko) 펩타이드가 결합된 재조합 엑소좀을 포함하는 rage 과발현에 의한 염증 매개 질환의 예방 또는 치료용 약학적 조성물
EP3672618A1 (fr) Compositions et méthodes d'administration d'agents pharmacologiques
Khodakarimi et al. Neurotrophic factors loaded TGN-modified chitosan nanoparticles ameliorate symptoms of MS through GATA3/FOXP3 and targeting Th1/2 cells pathways
TWI359030B (en) Treatment of cellular proliferative disorders
CN120641080A (zh) 包含十八碳神经肽(odn)及其合成衍生物的组合物以及用于调节食物摄入、肥胖、体重、恶心和呕吐的方法
JP2025540675A (ja) オクタデカニューロペプチド（ｏｄｎ）およびその合成誘導体を含む組成物、ならびに食物摂取、肥満、体重、吐き気および嘔吐の調節のための使用方法
US20240207361A1 (en) Erythropoietin-derived peptides for treating relapsing-remitting multiple sclerosis
JP2001524944A (ja) 神経障害性疼痛の緩和方法
Lanciego et al. Elisa Garbayo1, 2, Eduardo Ansorena2, 3, Hugo Lana1, 2, María del Mar Carmona-Abellan4, 5, Irene Marcilla5
EA043417B1 (ru) АГОНИСТ ДЛИТЕЛЬНОГО ДЕЙСТВИЯ GLP-1r КАК ТЕРАПИЯ ДЛЯ ЛЕЧЕНИЯ НЕВРОЛОГИЧЕСКИХ И НЕЙРОДЕГЕНЕРАТИВНЫХ ПАТОЛОГИЧЕСКИХ СОСТОЯНИЙ
Choi Glucagon-like peptide-1 delivery for treatment of type 2 diabetes

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24877973

Country of ref document: EP

Kind code of ref document: A1