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WO2025157289A1 - Composition pharmaceutique contenant un inhibiteur de prmt5 et un inhibiteur de krasg12c - Google Patents

Composition pharmaceutique contenant un inhibiteur de prmt5 et un inhibiteur de krasg12c

Info

Publication number
WO2025157289A1
WO2025157289A1 PCT/CN2025/074952 CN2025074952W WO2025157289A1 WO 2025157289 A1 WO2025157289 A1 WO 2025157289A1 CN 2025074952 W CN2025074952 W CN 2025074952W WO 2025157289 A1 WO2025157289 A1 WO 2025157289A1
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WO
WIPO (PCT)
Prior art keywords
cancer
alkyl
pharmaceutical composition
inhibitor
halo
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/CN2025/074952
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English (en)
Chinese (zh)
Inventor
毛伟峰
姚兵
朱利安 阿斯瓦德弗雷德
李铭曦
谷晓辉
约瑟夫詹姆斯大卫
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.)
Shanghai Apeiron Therapeutics Co Ltd
Original Assignee
Shanghai Apeiron Therapeutics Co Ltd
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 Shanghai Apeiron Therapeutics Co Ltd filed Critical Shanghai Apeiron Therapeutics Co Ltd
Publication of WO2025157289A1 publication Critical patent/WO2025157289A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention belongs to the field of medicine, and particularly relates to a pharmaceutical composition for protecting a PRMT5 inhibitor and a KRAS G12C inhibitor.
  • Cancer is a leading cause of death worldwide.
  • Popular treatments, such as chemotherapy and immunotherapy, are limited in that their cytotoxic effects are not restricted to cancer cells and can also cause adverse side effects in normal tissues.
  • the rat sarcoma (RAS) proto-oncogene has been identified as an oncogenic driver in cancers such as non-small cell lung cancer (NSCLC) and colorectal cancer (CRC).
  • the RAS family includes three closely related genes that express guanosine triphosphatase (GTPase) enzymes responsible for regulating cell proliferation and survival.
  • GTPase guanosine triphosphatase
  • the RAS proteins, Kirsten rat sarcoma viral oncogene homolog (KRAS), Harvey rat sarcoma viral oncogene homolog (HRAS), and neuroblastoma RAS viral oncogene homolog (NRAS) can be activated by mutations at codons 12, 13, or 61, leading to cancer in humans.
  • KRAS being the most frequently mutated isoform in most cancers.
  • anti-cancer therapies targeting KRAS mutations have been unsuccessful, primarily because the protein was considered refractory to inhibition by small molecules.
  • U.S. Sotorasib marketed under the name , is the first inhibitor of the RAS GTPase family and is indicated for adult patients with locally advanced or metastatic NSCLC harboring a KRAS G12C mutation who have received at least one prior systemic therapy. While sotorasib monotherapy appears to produce significant anti-tumor activity, combination therapies are desirable to further improve the treatment options available to patients.
  • PRMT5 is a type II arginine methyltransferase that regulates important cellular functions, including cell cycle progression, apoptosis, and the DNA damage response, by symmetrically dimethylating proteins involved in transcription and signal transduction.
  • data from genome-wide genetic perturbation screens using shRNA revealed a selective requirement for PRMT5 activity in MTAP-deleted cancer cell lines (Kruykov et al., 2016; Marjon et al., 2016; Markarov et al., 2016).
  • the accumulation of MTA caused by MTAP loss in these cell lines partially inhibits PRMT5, making these cells selectively sensitive to additional PRMT5 inhibition.
  • PRMT5 inhibitors have been developed, but they do not show selectivity for MTAP-deficient cancer cell lines. This lack of selectivity could be explained by the inhibitors’ mechanism of action, as they are either SAM-uncompetitive or SAM-competitive inhibitors and therefore independent of MTAP (Kruykov et al., 2016; Marjon et al., 2016 and Markarov et al., 2016).
  • PRMT5 inhibitors that bind non-competitively or cooperatively with MTA By using inhibitors that bind PRMT5 non-competitively or cooperatively with MTA, selectivity for MTAP-deficient/MTA-accumulating cells can be improved.
  • PRMT5 inhibitors that bind non-competitively or cooperatively with MTA will exhibit increased binding to PRMT5 in the presence of MTA compared to the binding of the same inhibitor in the absence of MTA. Consequently, such inhibitors will bind with significantly greater potency in the presence of high concentrations of MTA and, therefore, lead to preferential inhibition of PRMT5 in MTA-accumulating cells relative to normal cells.
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a PRMT5 inhibitor having a first active substance and a KRAS G12C inhibitor compound having a second active substance, wherein the PRMT5 inhibitor of the first active substance has the following structure of Formula (I) or Formula (II):
  • R 1 is selected from H, halogen, C 1 -C 6 alkyl, halo(C 1 -C 6 alkyl), CN;
  • R 2 is selected from H, C 1 -C 6 alkyl, halo(C 1 -C 6 alkyl), C 3 -C 6 cycloalkyl;
  • R 3 represents H, halogen, C 1 -C 6 alkyl, halo(C 1 -C 6 alkyl), halo(C 1 -C 6 alkoxy), or SF 5 ;
  • R 4 represents hydrogen or C 1 -C 6 alkyl
  • X represents CR 5 or N
  • R 5 represents hydrogen, halogen, C 1 -C 6 alkyl, halo(C 1 -C 6 alkyl), hydroxyl, -NH 2 , or CN.
  • R 1 is selected from hydrogen, halogen, C 1 -C 6 alkyl, halo(C 1 -C 6 alkyl);
  • R 2 is selected from hydrogen, C 1 -C 6 alkyl, halo(C 1 -C 6 alkyl), C 3 -C 6 cycloalkyl;
  • R 3 represents hydrogen, halogen, halo(C 1 -C 6 alkyl), halo(C 1 -C 6 alkoxy), or SF 5 ;
  • R 4 represents hydrogen or methyl
  • X represents CH or N.
  • R 1 is selected from hydrogen or fluorine.
  • R 2 is selected from cyclopropyl or methyl.
  • R 3 represents CF 3 .
  • R 4 represents hydrogen or methyl
  • X represents N.
  • the PRMT5 inhibitor of the first active substance is selected from the following compounds or any combination thereof:
  • the KRAS G12C inhibitor of the second active substance is selected from any one of the following compounds or their pharmaceutical salts: Adagrasib Sotorasib( and ), Divarasib (GDC-6036), Glecirasib (JAB-21822), LY3537982 (Eli Lilly and company), Garsorasib (D-1553), HBI-2438 (Huyabio International), Opnurasib (JDQ443), HS-10370 (Jiangsu Hansoh pharmaceutical company), IBI-351 (GFH925), BI-1823911 (Boehringer Ingelheim), JNJ-74699157 (ARS3248, Johnson & Johnson), RM-018 (Revolution Medicines), ARS-2102, RMC-4998, ASP2453, BI-2865, AZD4747, BI-0474, MK-108, BEBT-607, YL-15293, D3S-001, ABSK071, LY3499446,
  • the KRAS G12C inhibitor of the second active substance is selected from the Protac degrader LC2 (CAS: 2502156-03-6).
  • the KRAS G12C inhibitor of the second active substance is selected from Adagrasib Sotorasib( and ), Opnurasib (JDQ443), LY3537982 (Eli Lilly and company) or a pharmaceutically acceptable salt thereof.
  • the present disclosure also provides a method for treating cancer or tumor, comprising administering the pharmaceutical composition of the present invention to an individual in need thereof.
  • the tumor or cancer is selected from: glioblastoma multiforme, brain cancer, prostate cancer, pancreatic cancer, mantle cell lymphoma, non-Hodgkin's lymphoma and diffuse large B-cell lymphoma, acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma, non-small cell lung cancer, small cell lung cancer, breast cancer, triple-negative breast cancer, gastric cancer, colorectal cancer, ovarian cancer, bladder cancer, hepatocellular carcinoma, esophageal cancer, bile duct cancer, mesothelioma, laryngeal cancer, melanoma, malignant peripheral nerve sheath tumor, osteosarcoma, myxochondrosarcoma, soft tissue sarcoma, oropharyngeal squamous cell carcinoma, chronic myeloid leukemia, epidermal squamous cell carcinoma, nasopharyngeal
  • any feasible combination of a compound of formula (I) or a pharmaceutically acceptable salt, solvate or prodrug thereof and a compound of formula (II) or a pharmaceutically acceptable salt, solvate or prodrug thereof is included in the present invention, as long as such combination is capable of producing some synergistic effect in the treatment of a subject in need of such treatment.
  • any compound when used in the present invention, it includes any pharmaceutically acceptable form thereof, including but not limited to isomers, tautomers, salts, solvates, polymorphs, prodrugs, etc. It should be understood that the term “compound” includes any and all such forms, whether or not explicitly stated, although sometimes only certain terms are explicitly stated, such as “salt” and "prodrug”.
  • Alkoxy refers to a group -OR, where R is alkyl as defined herein. Representative examples include methoxy, ethoxy, propoxy, isopropoxy, sec-butoxy, tert-butoxy, and the like.
  • Alkyl refers to a group derived from a straight or branched chain saturated hydrocarbon by removing a hydrogen from one of the saturated carbons. Alkyl groups preferably contain 1 to 8 carbon atoms, sometimes preferably 1 to 6 carbon atoms, and sometimes even more preferably 1 to 4 carbon atoms. Representative examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, and the like. "Lower alkyl,” “lower alkoxy,” or “lower haloalkyl” refers to an alkyl or alkyl moiety having one to four, sometimes preferably one to three or one to two carbon atoms.
  • cyano refers to -CN.
  • cycloalkyl refers to a group derived from a monocyclic saturated carbocyclic ring by removing a hydrogen atom from the saturated carbocyclic ring, preferably having 3 to 8, more preferably 3 to 6 carbon atoms.
  • Representative examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclopentyl, and cyclohexyl.
  • halo and halogen refer to F, Cl, Br, or I.
  • haloalkyl refers to an alkyl group substituted with at least one halogen atom.
  • a haloalkyl group can be an alkyl group in which all hydrogen atoms are substituted with halogens.
  • Representative examples of haloalkyl groups include, but are not limited to, trifluoromethyl, fluoromethyl, difluoromethyl, bromomethyl, 1-chloroethyl, perchloroethyl, 2-fluoroethyl, etc.
  • heterocyclyl refers to a 3 to 10-membered monocyclic or bicyclic non-aromatic group containing one or more, preferably 1 to 3, heteroatoms independently selected from nitrogen (N), oxygen and sulfur (S, S(O) or S(O)2) in the non-aromatic ring.
  • the heterocyclyl of the present disclosure can be connected to the parent molecular moiety through a carbon atom or a nitrogen atom in the group.
  • the heterocyclyl group can be saturated or unsaturated, for example, containing one or more double bonds in the ring.
  • the valence of the group can be located on any atom of any ring within the group where the valence rules permit.
  • Examples may include, but are not limited to, azetidinyl, pyrrolidinyl, 2-oxopyrrolidinyl, 2,5-dihydro-1H-pyrrolyl, piperidinyl, 4-piperidinyl, morpholinyl, piperazinyl, 2-oxopiperazinyl, tetrahydropyranyl, tetrahydrofuranyl, 2-oxopiperidinyl, thiomorpholinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, etc.
  • any group such as “cycloalkyl” or “heterocyclyl” is referred to as “substituted or unsubstituted” or “optionally substituted”, unless otherwise specified, it means that the group is substituted or not substituted by 1 to 5, sometimes preferably 1 to 3 or 1 to 2 substituents independently selected from halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and cyano.
  • solvate refers to a physical association of a compound of the invention with one or more, preferably one to three, solvent molecules (whether organic or inorganic). This physical association includes hydrogen bonding. In some cases, the solvate is capable of separation, for example when one or more, preferably one to three, solvent molecules are incorporated into the crystal lattice of a crystalline solid. Exemplary solvates include, but are not limited to, hydrates, ethanolates, methanolates, and isopropanolates. Solvation methods are generally known in the art.
  • Prodrugs refer to compounds that can be converted in vivo to produce the active parent compound under physiological conditions, such as by hydrolysis in the blood. Common examples include, but are not limited to, ester and amide forms of compounds having an active form with a carboxylic acid moiety. Amides and esters of the compounds of the present invention can be prepared according to conventional methods. In particular, in the present invention, prodrugs can also be formed by acylation of the amino group or nitrogen atom in the heterocyclyl ring structure, where the acyl group can hydrolyze in vivo. Such acyl groups include, but are not limited to, C1-C6 acyl groups, preferably C1-C4 acyl groups, more preferably C1-C2 (formyl or acetyl) groups, or benzoyl groups.
  • the term "subject” refers to a human or other mammal, such as a monkey, dog, cat, horse, etc. The term is intended to encompass and is sometimes interchangeable with “patient.”
  • administering refers to providing a compound or pharmaceutical composition to a subject having or at risk for a disease or condition to be treated or prevented.
  • the compounds of the present invention can be administered to a subject in a solid dosage form such as a tablet, capsule, or the like.
  • the compounds of the present invention can be administered to a subject by intravenous injection.
  • the compounds of the present invention can be administered to a subject by any other suitable systemic delivery method, such as oral, parenteral, intranasal, sublingual, rectal, or transdermal administration.
  • the term "therapeutically effective amount” refers to that amount of a compound or composition that will elicit the desired or intended biological or medical response in a subject that is being sought by a physician, veterinarian, or researcher.
  • the therapeutically effective amount of the compound and the specific pharmaceutically acceptable carrier will vary depending on, for example, the age, weight, sex of the subject, the mode of administration, and the disease or condition being treated.
  • pharmaceutically acceptable when used before a compound, salt, prodrug, composition, or carrier means that such compound, salt, prodrug, composition, or carrier is suitable for administration to a subject for treatment without causing intolerable side effects to the subject considering the desired treatment.
  • the term "pharmaceutically acceptable carrier” refers to a substance that is compatible with the compounds used in the present invention and can be used to administer the compounds in the methods of the present invention, and is preferably non-toxic, or inert and pharmaceutically acceptable.
  • Pharmaceutically acceptable carriers can be solid, liquid or gaseous substances, including any and all dry powders, solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic agents, absorption delaying agents, and the like.
  • oils such as corn oil, buffers such as phosphate buffered saline (PBS), saline, polyethylene glycol, glycerol, polypropylene glycol, dimethyl sulfoxide, amides such as dimethylacetamide, proteins such as albumin, detergents such as Tween 80, monosaccharides and oligosaccharides such as glucose, lactose, cyclodextrins, starch, and the like.
  • PBS phosphate buffered saline
  • saline polyethylene glycol
  • glycerol polypropylene glycol
  • dimethyl sulfoxide dimethyl sulfoxide
  • amides such as dimethylacetamide
  • proteins such as albumin
  • detergents such as Tween 80
  • monosaccharides and oligosaccharides such as glucose, lactose, cyclodextrins, starch, and the like.
  • some embodiments of the compounds of the present invention can contain basic functional groups, such as amino or alkylamino, and therefore can form pharmaceutically acceptable salts with pharmaceutically acceptable acids.
  • pharmaceutically acceptable salts refers to relatively nontoxic inorganic and organic acid addition salts of the compounds of the present invention. These salts can be prepared on site during the administration of carriers or dosage form production processes, or by reacting the purified compounds of the present invention in free alkali form with suitable organic or inorganic acids alone, and separating the salts so formed in subsequent purification processes to prepare.
  • Representative salts include hydrobromide, hydrochloride, sulfate, bisulfate, phosphate, nitrate, acetate, valerate, oleate, palmitate, stearate, laurate, benzoate, lactate, phosphate, toluenesulfonate, citrate, maleate, fumarate, succinate.
  • formulations used in the present invention may also contain stabilizers, preservatives, buffers, antioxidants or other additives known to those skilled in the art.
  • stabilizers preservatives, buffers, antioxidants or other additives known to those skilled in the art.
  • antioxidants antioxidants or other additives known to those skilled in the art.
  • the use of such media and agents for pharmaceutically active substances is well known in the art.
  • synergistic refers to an effect caused by a combination of two or more agents that is greater than the cumulative effect of the two or more agents used alone.
  • This synergistic effect of combination therapy includes higher efficacy, lower side effects, or both.
  • the synergistic effect includes a significant reduction in the side effects of the two therapeutic inhibitors due to a reduction in the dosage of the two therapeutic inhibitors, while the overall therapeutic efficacy remains at approximately the same or improved levels.
  • the synergistic effect includes a significant improvement in the efficacy of inhibiting cancer cell proliferation, while the side effects caused by the two drugs remain at approximately the same or lower levels.
  • the synergistic effect allows the use of a lower dose of a single drug to effectively treat the disease.
  • the synergistic combination of two or more drugs can lead to improvements in disease treatment compared to monotherapy.
  • Combination therapy can allow the use of a lower dose of a first therapeutic agent, such as a PRMT5 inhibitor, or a second therapeutic agent, such as a MAT2A inhibitor, or lower doses of both therapeutic agents than would normally be required when either agent is used alone.
  • a first therapeutic agent such as a PRMT5 inhibitor
  • a second therapeutic agent such as a MAT2A inhibitor
  • the pharmaceutical composition may comprise a PRMT5 inhibitor and a KRAS G12C inhibitor for use in the methods of the present invention in a total amount of 0.01% to 99% by weight of the total composition, preferably 0.1% to 80% by weight of the total composition, and more preferably 0.1% to 50% by weight of the total composition.
  • the weight ratio between the PRMT5 inhibitor and the KRAS G12C inhibitor may be in the range of 1:20 to 20:1, sometimes preferably 1:15 to 15:1, and sometimes more preferably 1:10 to 10:1.
  • the daily dosage range for adult human treatment of a PRMT5 inhibitor is about 0.01 to about 150 mg/kg, preferably about 0.05 to about 100 mg/kg, and sometimes more preferably about 0.1 to about 50 mg/kg.
  • compositions that can be used to treat and/or prevent various cancers that may include or exclude the following cancers: glioblastoma multiforme, brain cancer, prostate cancer, pancreatic cancer, mantle cell lymphoma, non-Hodgkin lymphoma and diffuse large B-cell lymphoma, acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma, non-small cell lung cancer, small cell lung cancer, breast cancer, triple-negative breast cancer, gastric cancer, colorectal cancer, ovarian cancer, bladder cancer, hepatocellular carcinoma, esophageal cancer, bile duct cancer, mesothelioma, laryngeal cancer, melanoma, malignant peripheral nerve sheath tumor, osteosarcoma, myxochondrosarcoma, soft tissue sarcoma, oropharyngeal squamous cell carcinoma, chronic myeloid leukemia, epidermal squamous cell carcinoma
  • the cancer is metastatic cancer.
  • the metastatic cancer is brain metastatic cancer.
  • Figure 1A-1B Antitumor inhibition curves and inhibition rates of compound A, Divarasib, and their combination in the LU99 MTAP(-/-) deficient cell model
  • Figure 2A-2B Antitumor inhibition curves and inhibition rates of compound C, Divarasib, and their combination in the LU99 MTAP(-/-) deficient cell model
  • the LU99 MTAP (-/-) cell line was purchased from Beijing Kangyuan Bochuang Biotechnology Co., Ltd.
  • the cells were cultured in a cell culture medium containing 90% RPMI1640 and 10% fetal bovine serum at 37°C and 5% CO2. Experiments were performed only when the cells were in the logarithmic growth phase.
  • Cell inhibition rate (%) 100-(Lum test drug-Lum culture medium control)/(Lum solvent control-Lum culture medium control) ⁇ 100%
  • Example 1 Testing of single-drug compounds in the LU99 MTAP(-/-) deficient cell model
  • Table 1 shows the IC 20 and IC 50 of each compound in LU99 MTAP(-/-) deficient cells, as well as the maximum inhibition rate.
  • Example 2 Compound A combined with Divarasib in the LU99 MTAP(-/-) deficient cell model
  • FIG1B shows the inhibition rates of compound A (7.8 nM) and divarasib (0.7 nM) alone and in combination, indicating that the two compounds have a synergistic effect under these conditions.
  • Table 3 shows the combined effect index CI value of Compound A and Divarasib.
  • Example 3 Compound B combined with Divarasib in the LU99 MTAP(-/-) deficient cell model
  • FIG2B shows the inhibition rates of Divarasib (0.74 nM) and Compound C (7.8 nM) alone and in combination, indicating that under this condition, the two compounds have an additive effect.
  • Table 5 shows the combined effect index CI value of compound C and Divarasib.

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  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une composition pharmaceutique comprenant un inhibiteur de protéine arginine méthyltransférase 5 (PRMT5) et un inhibiteur de KRASG12C (glycine-en-cystéine d'homologue de l'oncogène viral du sarcome de rat de Kirsten). La composition pharmaceutique peut être utilisée pour traiter divers cancers, comprenant des tumeurs solides. Le produit combiné peut être utilisé pour traiter un nombre quelconque de maladies associées à PRMT5 et/ou KRASG12C.
PCT/CN2025/074952 2024-01-26 2025-01-24 Composition pharmaceutique contenant un inhibiteur de prmt5 et un inhibiteur de krasg12c Pending WO2025157289A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CN202410116131.X 2024-01-26
CN202410116131 2024-01-26
CN202410245529.3 2024-03-04
CN202410245529 2024-03-04

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WO2025157289A1 true WO2025157289A1 (fr) 2025-07-31

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12448388B2 (en) 2023-04-21 2025-10-21 Gilead Sciences, Inc. PRMT5 inhibitors and uses thereof

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CN114599361A (zh) * 2019-10-22 2022-06-07 印度鲁宾有限公司 Prmt5抑制剂的药物组合物
WO2022216648A1 (fr) * 2021-04-08 2022-10-13 Mirati Therapeutics, Inc. Polythérapies faisant appel à des inhibiteurs de prmt5 pour le traitement du cancer
WO2024002377A1 (fr) * 2022-07-01 2024-01-04 上海赛岚生物科技有限公司 Classe d'inhibiteurs de prmt5 et leur utilisation

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CN114599361A (zh) * 2019-10-22 2022-06-07 印度鲁宾有限公司 Prmt5抑制剂的药物组合物
WO2022216648A1 (fr) * 2021-04-08 2022-10-13 Mirati Therapeutics, Inc. Polythérapies faisant appel à des inhibiteurs de prmt5 pour le traitement du cancer
WO2024002377A1 (fr) * 2022-07-01 2024-01-04 上海赛岚生物科技有限公司 Classe d'inhibiteurs de prmt5 et leur utilisation
WO2024002376A1 (fr) * 2022-07-01 2024-01-04 上海赛岚生物科技有限公司 Inhibiteurs de prmt5 et leur utilisation

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BRIGGS K, G. CORRIEA , A. TSAI, M. ZHANG , M.R. TONINI , E.W. WILKER , C.B. DAVIS , K.M. COTTRELL , J.P. MAXWELL , A. HUANG: "24P Evidence for Synergy between TNG908, an MTAPnull-selective PRMT5 Inhibitor, and Sotorasib in an MTAPnull/ KRASG12C Xenograft Model", ANNALS OF ONCOLOGY, vol. 33, no. S1, 1 January 2022 (2022-01-01), pages S12 - S12, XP093339950, DOI: 10.1016/j.annonc.2022.01.032 *
SLEMMONS KATHERINE, BELMONTES BRIAN, LIU SIYUAN, MORIGUCHI JODI, POLICHENI ANTONIA, HUGHES PAUL E.: "Abstract 6246: The MTA-cooperative PRMT5 inhibitor AM-9747 exhibits robust antitumor activity in combination with clinically relevant chemotherapies and targeted agents in MTAP null tumor models", CANCER RESEARCH, vol. 83, no. 7_Supplement, 4 April 2023 (2023-04-04), pages 6246 - 6246, XP093339954, DOI: 10.1158/1538-7445.AM2023-6246 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12448388B2 (en) 2023-04-21 2025-10-21 Gilead Sciences, Inc. PRMT5 inhibitors and uses thereof

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