JP6936498B2 - 抗アポトーシス性Ｂｃｌ−２ファミリータンパク質の分解を誘導する化合物及びその使用 - Google Patents

抗アポトーシス性Ｂｃｌ−２ファミリータンパク質の分解を誘導する化合物及びその使用 Download PDF

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JP6936498B2
JP6936498B2 JP2018555177A JP2018555177A JP6936498B2 JP 6936498 B2 JP6936498 B2 JP 6936498B2 JP 2018555177 A JP2018555177 A JP 2018555177A JP 2018555177 A JP2018555177 A JP 2018555177A JP 6936498 B2 JP6936498 B2 JP 6936498B2
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グアンロン・ジェン
ダオホン・ジョウ
シュアン・ジャン
インイン・ワン
ジエンホイ・チャン
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Neurology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Neurosurgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
JP2018555177A 2016-04-21 2017-04-21 抗アポトーシス性Ｂｃｌ−２ファミリータンパク質の分解を誘導する化合物及びその使用 Active JP6936498B2 (ja)

Applications Claiming Priority (3)

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US201662325856P 2016-04-21 2016-04-21
US62/325,856 2016-04-21
PCT/US2017/028875 WO2017184995A1 (en) 2016-04-21 2017-04-21 Compounds that induce degradation of anti-apoptotic bcl-2 family proteins and the uses thereof

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JP2019514877A JP2019514877A (ja) 2019-06-06
JP2019514877A5 JP2019514877A5 (cg-RX-API-DMAC7.html) 2020-06-11
JP6936498B2 true JP6936498B2 (ja) 2021-09-15

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US (2) US10807977B2 (cg-RX-API-DMAC7.html)
EP (1) EP3445452A4 (cg-RX-API-DMAC7.html)
JP (1) JP6936498B2 (cg-RX-API-DMAC7.html)
KR (1) KR102447884B1 (cg-RX-API-DMAC7.html)
CN (1) CN109152933B (cg-RX-API-DMAC7.html)
AU (1) AU2017254687B2 (cg-RX-API-DMAC7.html)
CA (1) CA3018991A1 (cg-RX-API-DMAC7.html)
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Families Citing this family (54)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3708170A1 (en) 2014-05-05 2020-09-16 BioVentures, LLC Compositions and methods for inhibiting antiapoptotic bcl-2 proteins as anti-aging agents
WO2016014625A1 (en) 2014-07-22 2016-01-28 Board Of Trustees Of The University Of Arkansas Compositions and methods for selectively depleting senescent cells
CA3018991A1 (en) * 2016-04-21 2017-10-26 Bioventures, Llc Compounds that induce degradation of anti-apoptotic bcl-2 family proteins and the uses thereof
PL3660004T3 (pl) 2016-10-11 2023-10-02 Arvinas Operations, Inc. Związki i sposoby do ukierunkowanej degradacji receptora androgenowego
IL290809B2 (en) 2016-11-01 2024-01-01 Arvinas Operations Inc Tau-protein targeting protacs and associated methods of use
KR102656934B1 (ko) 2017-07-10 2024-04-16 셀진 코포레이션 항증식성 화합물 및 이의 사용 방법
KR20200108298A (ko) 2018-01-10 2020-09-17 리커리엄 아이피 홀딩스, 엘엘씨 벤즈아미드 화합물
CA3088253A1 (en) * 2018-01-22 2019-07-25 Bioventures, Llc Bcl-2 proteins degraders for cancer treatment
US12084423B2 (en) 2018-05-18 2024-09-10 Bioventures, Llc Piperlongumine analogues and uses thereof
WO2019218904A1 (zh) * 2018-05-18 2019-11-21 四川科伦博泰生物医药股份有限公司 非天然氨基酸类衍生物、其制备方法及用途
EP3790861A4 (en) * 2018-07-11 2022-03-30 Rubedo Life Sciences, Inc. SENOLYTIC COMPOSITIONS AND THEIR USES
US20220169628A1 (en) * 2019-02-08 2022-06-02 University Of Florida Research Foundation, Incorporated Therapeutic agents and methods of treatment
CN114144411A (zh) * 2019-07-10 2022-03-04 里科瑞尔姆Ip控股有限责任公司 Bcl-2蛋白抑制剂
JP7548992B2 (ja) * 2019-07-17 2024-09-10 アルビナス・オペレーションズ・インコーポレイテッド タウタンパク質標的化化合物および関連する使用方法
EP4038066A1 (en) * 2019-10-01 2022-08-10 Arvinas Operations, Inc. Brm targeting compounds and associated methods of use
CN112707900B (zh) * 2019-10-24 2022-06-10 上海科技大学 蛋白降解剂及其在疾病治疗中的应用
WO2021126973A1 (en) * 2019-12-17 2021-06-24 Orionis Biosciences, Inc. Compounds modulating protein recruitment and/or degradation
WO2021146536A1 (en) * 2020-01-15 2021-07-22 University Of Florida Research Foundation, Incorporated Therapeutic agents and methods of treatment
WO2021180040A1 (zh) * 2020-03-12 2021-09-16 南京明德新药研发有限公司 苯并五元环类化合物
KR20230002483A (ko) * 2020-04-28 2023-01-05 리커리엄 아이피 홀딩스, 엘엘씨 Bcl-2 단백질 억제제
JP2023524599A (ja) 2020-05-09 2023-06-12 アルビナス・オペレーションズ・インコーポレイテッド 二官能性化合物を製造する方法、二官能性化合物の超高純度形態、及びそれらを含む剤形
JP2024504932A (ja) 2021-01-13 2024-02-02 モンテ ローザ セラピューティクス， インコーポレイテッド イソインドリノン化合物
IL304891A (en) 2021-02-02 2023-10-01 Servier Lab Selective Protech BCL-XL compounds and methods of use
WO2022236058A1 (en) 2021-05-07 2022-11-10 Kymera Therapeutics, Inc. Cdk2 degraders and uses thereof
WO2022255888A1 (en) * 2021-06-01 2022-12-08 Captor Therapeutics S.A. Targeted protein degradation using bifunctional compounds that bind ubiquitin ligase and target mcl-1 protein
CN117897385A (zh) * 2021-09-01 2024-04-16 西藏海思科制药有限公司 一种降解Bcl-2家族蛋白的化合物及其在医药上的应用
US20250197387A1 (en) * 2021-09-17 2025-06-19 Kymera Therapeutics, Inc. Bcl-xl degraders and uses thereof
TW202320769A (zh) * 2021-11-17 2023-06-01 大陸商成都先導藥物開發股份有限公司 一種降解劑及其用途
US20250154146A1 (en) * 2022-01-04 2025-05-15 Shanghaitech University Protein degraders developed on basis of bcl-2 family protein ligand compounds and use thereof
WO2023205802A2 (en) * 2022-04-22 2023-10-26 Sens Research Foundation Senolytic targets of senescent cells
PE20250007A1 (es) 2022-05-06 2025-01-07 Treeline Biosciences Inc Degradadores bcl-xl-heterobifuncionales de tetrahidroisoquinolina
US20250282771A1 (en) 2022-05-06 2025-09-11 Treeline Biosciences, Inc. Tetrahydroisoquinoline heterobifunctional bcl-xl degraders
EP4519272A1 (en) 2022-05-06 2025-03-12 Treeline Biosciences, Inc. Tetrahydroisoquinoline heterobifunctional bcl-xl degraders
CN119768402A (zh) * 2022-07-12 2025-04-04 正大天晴药业集团股份有限公司 含有三氟甲基基团的化合物
WO2024027706A1 (en) * 2022-08-02 2024-02-08 Beijing Neox Biotech Limited Bcl-xl degrading compounds
CN115141198A (zh) * 2022-09-01 2022-10-04 上海睿跃生物科技有限公司 降解蛋白的化合物及其应用和药物
CN119923390A (zh) * 2022-09-06 2025-05-02 西藏海思科制药有限公司 一种抑制Bcl-2或Bcl-xL的化合物及其在医药上的应用
CN115286689B (zh) * 2022-09-29 2023-01-06 上海睿跃生物科技有限公司 靶向降解Bcl-2蛋白的化合物及其应用和药物
CN115260191B (zh) * 2022-09-29 2022-12-27 上海睿跃生物科技有限公司 哌啶类化合物及其制备方法和应用
WO2024067818A1 (zh) * 2022-09-30 2024-04-04 江苏恒瑞医药股份有限公司 一种用于bcl-2蛋白靶向降解的嵌合体化合物、其制备方法及其在医药上的应用
CN115286630B (zh) * 2022-10-09 2022-12-27 上海睿跃生物科技有限公司 哌嗪类化合物及其制备方法和应用
WO2024078581A1 (en) * 2022-10-12 2024-04-18 Appicine Therapeutics (Hk) Limited Selective bcl-xl protac compounds and uses thereof
WO2024123195A1 (en) * 2022-12-06 2024-06-13 Captor Therapeutics S.A. Targeted protein degradation using prodrugs of bifunctional compounds that bind ubiquitin ligase and target mcl-1 protein
AU2023389065A1 (en) * 2022-12-06 2025-06-19 Captor Therapeutics S.A. Targeted protein degradation using bifunctional compounds that bind ubiquitin ligase and target mcl-1 protein
KR20250142929A (ko) * 2023-02-17 2025-09-30 치아타이 티안큉 파마수티컬 그룹 주식회사 트리플루오로메틸설포닐을 포함하는 화합물
WO2024245312A1 (en) * 2023-05-30 2024-12-05 Ascentage Pharma (Suzhou) Co., Ltd. Bcl-2/bcl-xl protein degrader and use thereof
TW202527930A (zh) 2023-11-07 2025-07-16 美商樹線生物科學公司 四氫異喹啉異雙功能ｂｃｌ－ｘｌ降解劑
WO2025101571A1 (en) 2023-11-07 2025-05-15 Treeline Biosciences, Inc. Tetrahydroisoquinoline heterobifunctional bcl-x l degraders
WO2025101575A1 (en) 2023-11-07 2025-05-15 Treeline Biosciences, Inc. Tetrahydroisoquinoline heterobifunctional bcl-x l degraders
US20250171473A1 (en) * 2023-11-27 2025-05-29 Rubedo Life Sciences, Inc. Phosphorous Containing BCL Inhibitors and Senolytic Compounds and Uses Thereof
US12496301B2 (en) 2023-12-08 2025-12-16 Arvinas Operations, Inc. Use of androgen receptor degrader for the treatment of spinal and bulbar muscular atrophy
WO2025136208A1 (en) 2023-12-21 2025-06-26 Hadjab Saida Senolytic compounds for use in the treatment and/or prevention of a headache disorder and/or chronic pain
CN117624134B (zh) * 2024-01-26 2024-05-03 南昌市第一医院 一种靶向降解hdac4的化合物及其制备方法和应用
CN118908940B (zh) * 2024-10-11 2024-12-31 齐鲁理工学院 一种靶向抗凋亡Bcl-2的蛋白水解靶向嵌合体的制备和应用

Family Cites Families (80)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4394448A (en) 1978-02-24 1983-07-19 Szoka Jr Francis C Method of inserting DNA into living cells
US4529561A (en) 1978-03-24 1985-07-16 The Regents Of The University Of California Method for producing liposomes in selected size range
US4241046A (en) 1978-11-30 1980-12-23 Papahadjopoulos Demetrios P Method of encapsulating biologically active materials in lipid vesicles
US4925661A (en) 1984-04-19 1990-05-15 Leaf Huang Target-specific cytotoxic liposomes
US4957735A (en) 1984-06-12 1990-09-18 The University Of Tennessee Research Corporation Target-sensitive immunoliposomes- preparation and characterization
US4755388A (en) 1984-11-09 1988-07-05 The Regents Of The University Of California Liposome-encapsulated 5-fluoropyrimidines and methods for their use
DE3542773A1 (de) 1985-12-04 1987-06-11 Roehm Pharma Gmbh Hautwirksame pharmaka mit liposomen als wirkstofftraeger
US4828837A (en) 1987-03-30 1989-05-09 Liposome Technology, Inc. Non-crystalline minoxidil composition, its production and application
US5077211A (en) 1988-07-06 1991-12-31 Applied Genetics, Inc. Purification and administration of dna repair enzymes
US5223409A (en) 1988-09-02 1993-06-29 Protein Engineering Corp. Directed evolution of novel binding proteins
US5043164A (en) 1989-01-17 1991-08-27 The University Of Tennessee Research Corporation Blood-stable, cholesterol-free liposomes
US5064655A (en) 1989-02-24 1991-11-12 Liposome Technology, Inc. Liposome gel composition and method
US5744101A (en) 1989-06-07 1998-04-28 Affymax Technologies N.V. Photolabile nucleoside protecting groups
US5264618A (en) 1990-04-19 1993-11-23 Vical, Inc. Cationic lipids for intracellular delivery of biologically active molecules
DE69217783T2 (de) 1991-04-05 1997-08-07 Kanegafuchi Chemical Ind 3-Phenoxybenzyl(iden)pyrrolidin-Derivate, deren Herstellung und deren Verwendung als muskarin-cholinerge Mittel
US5491069A (en) 1994-02-18 1996-02-13 The Regents Of The University Of California Biomarkers of cell senescence
US5888764A (en) 1995-01-20 1999-03-30 Uab Research Foundation Human fas gene promoter region
DE19713393C2 (de) 1997-04-01 2002-12-05 Apotech Res & Dev Ltd Flip-Gen und Flip-Protein
JPH11349568A (ja) 1998-06-08 1999-12-21 Maruho Co Ltd ラクタム誘導体及びその医薬用途
WO2000004901A1 (en) 1998-07-21 2000-02-03 Thomas Jefferson University Small molecule inhibitors of bcl-2 proteins
AUPR038200A0 (en) 2000-09-26 2000-10-19 Beta Peptide Foundation Pty Ltd, The Compositions and methods for delaying, preventing, rejuvenating or reversing senescence
ATE474568T1 (de) 2001-05-30 2010-08-15 Univ Michigan Synergistische kombination von (-) -gossypol mit docetaxel oder paclitaxel zur behandlung von krebs.
PT1788394E (pt) 2002-05-07 2009-08-13 Pasteur Institut Rastreio de péptidos que inibem a ligação da pp1c às proteínas bcl-2, bcl-xi e bcl-w
AU2003245436A1 (en) 2003-01-23 2004-08-23 The Trustees Of Columbia University In The City Of New York Old-35, a gene associated with senescence and terminal cell differentiation, and uses thereof
PT1644363E (pt) 2003-05-30 2012-05-18 Gemin X Pharmaceuticals Canada Inc Compostos tri-heterocíclicos, composições e métodos para tratamento de cancro ou doenças virais
WO2005042002A2 (en) 2003-10-30 2005-05-12 Entelos, Inc. Treatment of rhematoid arthritis with flip antagonists
US7973161B2 (en) 2003-11-13 2011-07-05 Abbott Laboratories Apoptosis promoters
CA2545006C (en) 2003-12-12 2013-09-17 Saint Louis University Biosensors for detecting macromolecules and other analytes
KR100966749B1 (ko) 2004-05-26 2010-06-30 에자이 알앤드디 매니지먼트 가부시키가이샤 신나미드 화합물
BRPI0514504A (pt) 2004-08-20 2008-06-10 Univ Michigan pequenas moléculas inibidoras de membros da famìlia bcl-2 anti-apoptóticos e os usos das mesmas
CA2606147C (en) 2005-05-12 2011-07-05 Abbott Laboratories Apoptosis promoters
US20100093613A1 (en) 2007-03-09 2010-04-15 Kunkel Eric J Methods for identifying agents and their use for the prevention or stabilization of fibrosis
BRPI0810082A2 (pt) 2007-03-29 2014-10-21 Novartis Ag 3-imidazolil-indóis para o tratamento de doenças proliferativas
US20100310504A1 (en) 2007-09-26 2010-12-09 Lowe Scott W Methods for treating fibrosis by modulating cellular senescence
US20120156134A1 (en) 2007-12-20 2012-06-21 Shayne Squires Compositions and methods for detecting or eliminating senescent cells to diagnose or treat disease
WO2009114126A1 (en) 2008-03-11 2009-09-17 The General Hospital Corporation Piperlongumine and piperlongumine analogs for use in the treatment of cancer
US8168784B2 (en) 2008-06-20 2012-05-01 Abbott Laboratories Processes to make apoptosis promoters
US20100086941A1 (en) 2008-10-01 2010-04-08 Adami Guy R Methods for determining aged based accumulation of senescent cells using senescence specific DNA damage markers
WO2010080478A1 (en) 2008-12-19 2010-07-15 Genentech, Inc. Compounds and methods of use
WO2010080503A1 (en) 2008-12-19 2010-07-15 Genentech, Inc. Heterocyclic compounds and methods of use
CN102395268A (zh) 2009-04-15 2012-03-28 桑福德-伯纳姆医学研究院 基于萘的抗凋亡蛋白抑制剂
PL2435432T6 (pl) 2009-05-26 2024-02-12 Abbvie Ireland Unlimited Company Środki wywołujące apoptozę do leczenia raka oraz chorób immunologicznych i autoimmunologicznych
EP2289528A1 (en) 2009-07-21 2011-03-02 DSM IP Assets B.V. Novel nutraceutical compositions containing black pepper or its constituents improving mental performance
US8318737B2 (en) 2009-09-02 2012-11-27 Canthera Therapeutics Inc. Compounds and compositions for treating cancer
US20120157455A1 (en) 2009-09-02 2012-06-21 Canthera Therapeutics, Inc. Compounds And Compositions For Treating Cancer
US8349832B2 (en) 2009-09-02 2013-01-08 Canthera Therapeutics Compounds and compositions for treating cancer
EP2519260A2 (en) 2009-12-31 2012-11-07 Deutsches Krebsforschungszentrum Novel modulators of trail signalling
CN101774875A (zh) 2010-01-08 2010-07-14 北京欧凯纳斯科技有限公司 一种荜拔酰胺类化合物的合成方法
CN102125552A (zh) 2010-01-20 2011-07-20 李绍路 荜茇酰胺衍生物在制备治疗癌症的药物中的用途及其药物组合物
CN102146054A (zh) 2010-02-10 2011-08-10 新昌县来益科技开发有限公司 荜茇酰胺衍生物及其药物组合物和在制备抑制肿瘤生长的药物中的用途
WO2011130395A1 (en) 2010-04-13 2011-10-20 University Of Utah Research Foundation Inhibitors of flip to treat cancer
UY33746A (es) * 2010-11-23 2012-06-29 Abbott Lab Método de tratamiento que usa inhibidores selectivos de bcl-2
AU2012209295B2 (en) * 2011-01-25 2016-06-30 The Regents Of The University Of Michigan Bcl-2/Bcl-xL inhibitors and therapeutic methods using the same
CN103958508B (zh) * 2011-10-14 2019-02-12 艾伯维公司 用于治疗癌症以及免疫与自身免疫性疾病的细胞凋亡诱导剂
EP2602330A1 (en) 2011-12-07 2013-06-12 Palacky University, Olomouc Method of determination of cancer cell drug sensitivity towards Aurora kinase inhibitors and overcoming their resistance
EP2802608A4 (en) * 2012-01-12 2015-08-05 Univ Yale COMPOUNDS AND METHODS FOR ENHANCED DEGRADATION OF TARGET PROTEINS AND OTHER POLYPEPTIDES BY E3 UBIQUITIN LIGASE
HK1204928A1 (en) 2012-06-01 2015-12-11 Leibniz-Institut Für Altersforschung - Fritz-Lipmann-Institut E.V. Inhibitors of the notch signalling pathway and secretion for use in medicine
US9108923B2 (en) 2012-07-20 2015-08-18 Howard Hughes Medical Institute Compounds, compositions, and methods for cancer therapy
CN103601670B (zh) 2012-11-20 2016-06-15 中国人民解放军第二军医大学 荜拔酰胺类似物及其制备方法与应用
US10279018B2 (en) 2012-12-03 2019-05-07 Unity Biotechnology, Inc. Immunogenic compositions for inducing an immune response for elimination of senescent cells
GB201311910D0 (en) 2013-07-03 2013-08-14 Glaxosmithkline Ip Dev Ltd Novel Compounds
KR102318204B1 (ko) * 2013-01-16 2021-10-26 더 리젠츠 오브 더 유니버시티 오브 미시간 Bcl-2bcl-xl 억제제 및 그를 사용하는 치료 방법
US20160122758A1 (en) 2013-04-21 2016-05-05 Yeda Research And Development Co. Ltd. Agents for downregulation of the activity and/or amount of bcl-xl and/or bcl-w
RU2716256C2 (ru) * 2014-01-28 2020-03-11 Бак Инститьют Фо Ресеч Он Эйджинг Способы и композиции для уничтожения стареющих клеток и для лечения заболеваний и расстройств, ассоциированных со старением
EP4649963A2 (en) * 2014-04-14 2025-11-19 Arvinas Operations, Inc. Imide-based modulators of proteolysis and associated methods of use
EP3708170A1 (en) 2014-05-05 2020-09-16 BioVentures, LLC Compositions and methods for inhibiting antiapoptotic bcl-2 proteins as anti-aging agents
WO2016014625A1 (en) 2014-07-22 2016-01-28 Board Of Trustees Of The University Of Arkansas Compositions and methods for selectively depleting senescent cells
US10071164B2 (en) 2014-08-11 2018-09-11 Yale University Estrogen-related receptor alpha based protac compounds and associated methods of use
US9694084B2 (en) 2014-12-23 2017-07-04 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
WO2016118855A1 (en) 2015-01-22 2016-07-28 Board Of Trustees Of The University Of Arkansas Compositions and methods for selectively depleting senescent cells comprising death receptors
US20180021323A1 (en) 2015-01-22 2018-01-25 Bioventures, Llc Flip - a selective molecular target of senescent cells
US20180000816A1 (en) * 2015-02-06 2018-01-04 Unity Biotechnology, Inc. Use of a Heterocyclic Bcl-xL Inhibitor and Related Analogs for Removing Senescent Cells in the Treatment of Eye Diseases and Other Age-Related Conditions
AU2016232705C1 (en) * 2015-03-18 2021-06-17 Arvinas, Inc. Compounds and methods for the enhanced degradation of targeted proteins
CN105085620B (zh) 2015-06-25 2018-05-08 中山大学附属第一医院 一种靶向泛素化降解Smad3的化合物
US11179348B2 (en) 2015-07-21 2021-11-23 Fundación Universidad Católica De Valencia San Vicente Mártir Combination comprising pterostilbene for the treatment of cancer
WO2017030814A1 (en) * 2015-08-19 2017-02-23 Arvinas, Inc. Compounds and methods for the targeted degradation of bromodomain-containing proteins
US11111259B2 (en) 2015-12-18 2021-09-07 Unity Biotechnology, Inc. Acylsulfonamide derivatives for treating senescence-associated diseases and disorders
US20190054097A1 (en) 2016-04-21 2019-02-21 Bioventures, Llc Compositions targeting senescent cells and the uses thereof
CA3018991A1 (en) 2016-04-21 2017-10-26 Bioventures, Llc Compounds that induce degradation of anti-apoptotic bcl-2 family proteins and the uses thereof
CA3088253A1 (en) * 2018-01-22 2019-07-25 Bioventures, Llc Bcl-2 proteins degraders for cancer treatment

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US20200331905A1 (en) 2020-10-22
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JP2019514877A (ja) 2019-06-06
CN109152933B (zh) 2022-12-02
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