AU2017254687B2 - Compounds that induce degradation of anti-apoptotic Bcl-2 family proteins and the uses thereof - Google Patents

Compounds that induce degradation of anti-apoptotic Bcl-2 family proteins and the uses thereof Download PDF

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AU2017254687B2
AU2017254687B2 AU2017254687A AU2017254687A AU2017254687B2 AU 2017254687 B2 AU2017254687 B2 AU 2017254687B2 AU 2017254687 A AU2017254687 A AU 2017254687A AU 2017254687 A AU2017254687 A AU 2017254687A AU 2017254687 B2 AU2017254687 B2 AU 2017254687B2
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bcl
bond
cells
formula
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AU2017254687A1 (en
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Jianhui CHANG
Yingying Wang
Xuan Zhang
Guangrong Zheng
Daohong Zhou
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BioVentures LLC
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    • 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
    • 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
    • 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)
AU2017254687A 2016-04-21 2017-04-21 Compounds that induce degradation of anti-apoptotic Bcl-2 family proteins and the uses thereof Active AU2017254687B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
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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AU2017254687A1 AU2017254687A1 (en) 2018-10-18
AU2017254687B2 true AU2017254687B2 (en) 2021-09-30

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US (2) US10807977B2 (https=)
EP (1) EP3445452A4 (https=)
JP (1) JP6936498B2 (https=)
KR (1) KR102447884B1 (https=)
CN (1) CN109152933B (https=)
AU (1) AU2017254687B2 (https=)
WO (2) WO2017184995A1 (https=)

Families Citing this family (55)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3139942B1 (en) 2014-05-05 2019-12-18 Bioventures, Llc COMPOSITIONS AND METHODS FOR INHIBITING ANTIAPOPTOTIC Bcl-2 PROTEINS AS ANTI-AGING AGENTS
US10071087B2 (en) 2014-07-22 2018-09-11 Bioventures, Llc Compositions and methods for selectively depleting senescent cells
JP6936498B2 (ja) 2016-04-21 2021-09-15 バイオベンチャーズ・リミテッド・ライアビリティ・カンパニーＢｉｏＶｅｎｔｕｒｅｓ， ＬＬＣ 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
WO2018071606A1 (en) 2016-10-11 2018-04-19 Arvinas, Inc. Compounds and methods for the targeted degradation of androgen receptor
IL290809B2 (en) 2016-11-01 2024-01-01 Arvinas Operations Inc Tau-protein targeting protacs and associated methods of use
TWI791552B (zh) 2017-07-10 2023-02-11 美商西建公司 抗增生化合物及其使用方法
EP3737681A4 (en) 2018-01-10 2022-01-12 Recurium IP Holdings, LLC BENZAMIDE COMPOUNDS
EP3743069B1 (en) * 2018-01-22 2025-08-06 BioVentures, LLC Bcl-2 proteins degraders for cancer treatment
US12539292B2 (en) 2018-04-01 2026-02-03 Arvinas Operations, Inc. BRM targeting compounds and associated methods of use
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
IL312612A (en) * 2018-07-11 2024-07-01 Rubedo Life Sciences Inc Senolytic compositions and uses thereof
WO2020163823A2 (en) * 2019-02-08 2020-08-13 University Of Florida Research Foundation, Incorporated Therapeutic agents and methods of treatment
WO2021007307A1 (en) * 2019-07-10 2021-01-14 Recurium Ip Holdings, Llc Bcl-2 protein inhibitors
CN119954801A (zh) 2019-07-17 2025-05-09 阿尔维纳斯运营股份有限公司 Tau蛋白靶向化合物及相关使用方法
EP4038066A1 (en) * 2019-10-01 2022-08-10 Arvinas Operations, Inc. Brm targeting compounds and associated methods of use
WO2021078301A1 (zh) * 2019-10-24 2021-04-29 上海科技大学 蛋白降解剂及其在疾病治疗中的应用
JP2023507590A (ja) * 2019-12-17 2023-02-24 オリオニス バイオサイエンシズ，インコーポレイテッド タンパク質の動員および／または分解を調節する化合物
AU2021207672A1 (en) 2020-01-15 2022-07-14 University Of Florida Research Foundation, Incorporated Therapeutic agents and methods of treatment
US20230128137A1 (en) * 2020-03-12 2023-04-27 Medshine Discovery Inc. Benzo five-membered cyclic compound
MX2022010512A (es) * 2020-04-28 2022-11-16 Recurium Ip Holdings Llc Inhibidores de proteína bcl-2.
CN115996918A (zh) 2020-05-09 2023-04-21 阿尔维纳斯运营股份有限公司 制造双官能团化合物的方法、双官能团化合物的超纯形式以及包括所述双官能团化合物的剂型
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
CN117794929A (zh) 2021-02-02 2024-03-29 法国施维雅药厂 选择性bcl-xl protac化合物及使用方法
AU2022271290A1 (en) 2021-05-07 2023-11-23 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
CA3231175A1 (en) * 2021-09-01 2023-03-09 Xizang Haisco Pharmaceutical Co., Ltd. Compound for degradation of bcl-2 family proteins and medical application thereof
EP4401729A4 (en) * 2021-09-17 2025-10-01 Kymera Therapeutics Inc BCL-XL DEGRADING AGENTS AND THEIR USES
WO2023088245A1 (zh) * 2021-11-17 2023-05-25 成都先导药物开发股份有限公司 一种降解剂及其用途
EP4461730A4 (en) * 2022-01-04 2025-12-24 Univ Shanghai Technology PROTEIN DEGRADING AGENTS DEVELOPED BASED ON BCL-2 FAMILY PROTEIN LIGAND COMPOUNDS AND THEIR USE
WO2023205802A2 (en) * 2022-04-22 2023-10-26 Sens Research Foundation Senolytic targets of senescent cells
US20250282771A1 (en) 2022-05-06 2025-09-11 Treeline Biosciences, Inc. Tetrahydroisoquinoline heterobifunctional bcl-xl degraders
JP2025516359A (ja) 2022-05-06 2025-05-27 ツリーライン バイオサイエンシズ インコーポレイテッド テトラヒドロイソキノリンヘテロ二官能性ｂｃｌ－ｘｌ分解剤
PE20250007A1 (es) 2022-05-06 2025-01-07 Treeline Biosciences Inc Degradadores bcl-xl-heterobifuncionales de tetrahidroisoquinolina
WO2024012449A1 (zh) * 2022-07-12 2024-01-18 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
EP4565236A1 (en) * 2022-08-02 2025-06-11 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
WO2024051741A1 (zh) * 2022-09-06 2024-03-14 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
JP2025540970A (ja) * 2022-12-06 2025-12-17 キャプター セラピューティクス エス．エー． ユビキチンリガーゼ及びターゲットｍｃｌ－１タンパク質に結合する二機能性化合物を使用するターゲティングされたタンパク質分解
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
JP2026507476A (ja) * 2023-02-17 2026-03-04 チア タイ ティエンチン ファーマシューティカル グループ カンパニー リミテッド トリフルオロメタンスルホニル基を含む化合物
EP4719408A1 (en) * 2023-05-30 2026-04-08 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
WO2025101575A1 (en) 2023-11-07 2025-05-15 Treeline Biosciences, Inc. Tetrahydroisoquinoline heterobifunctional bcl-x l degraders
WO2025101571A1 (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

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20150291562A1 (en) * 2014-04-14 2015-10-15 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use

Family Cites Families (79)

* 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
EP0532767B1 (en) 1991-04-05 1997-03-05 Kanegafuchi Kagaku Kogyo Kabushiki Kaisha 3-Phenoxybenzyl(idene)pyrrolidine derivatives, their preparation and their use as muscarinic cholinergic agents
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
EP1100496A4 (en) 1998-07-21 2002-10-23 Univ Jefferson SMALL MOLECULES INHIBIT THE 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
AU2002305769B2 (en) 2001-05-30 2007-07-19 Georgetown University Small molecule antagonists of Bcl2 family proteins
ES2327773T3 (es) 2002-05-07 2009-11-03 Institut Pasteur Seleccion de peptidos que unhiben la union de pp1c a proteinas bcl-2, bcl-xl y bcl-w.
WO2004066915A2 (en) 2003-01-23 2004-08-12 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
CN1832939B (zh) 2003-05-30 2010-04-28 杰明X医药品加拿大公司 用于治疗癌症或病毒病的三杂环化合物、组合物和方法
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
CN101208437B (zh) 2003-12-12 2012-07-04 圣路易斯大学 检测大分子和其它分析物的生物传感器
MY149038A (en) 2004-05-26 2013-07-15 Eisai R&D Man Co Ltd Cinnamide compound
CA2577752A1 (en) 2004-08-20 2006-03-02 The Regents Of The University Of Michigan Small molecule inhibitors of anti-apoptotic bcl-2 family members and the uses thereof
EP1888550B1 (en) 2005-05-12 2014-06-25 AbbVie Bahamas Ltd. 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
CA2682483A1 (en) 2007-03-29 2008-10-09 Novartis Ag 3-imidazolyl-indoles for the treatment of proliferative diseases
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
CA2718400A1 (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
US8232273B2 (en) 2008-12-19 2012-07-31 Genentech, Inc. Heterocyclic compounds and methods of use
RU2561109C2 (ru) 2008-12-19 2015-08-20 Дженентек, Инк. Соединения и способы применения
BRPI1016102A2 (pt) 2009-04-15 2015-09-01 Sanford Burhnham Medical Res Inst Inibidores de proteínas anti-apoptótica baseados em naftaleno
NZ595708A (en) * 2009-05-26 2014-03-28 Abbvie Bahamas Ltd Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
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
US20120157455A1 (en) 2009-09-02 2012-06-21 Canthera Therapeutics, Inc. Compounds And Compositions For Treating Cancer
US8318737B2 (en) 2009-09-02 2012-11-27 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
WO2011080314A2 (en) 2009-12-31 2011-07-07 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
TWI620736B (zh) 2010-11-23 2018-04-11 艾伯維巴哈馬有限公司 使用選擇性ｂｃｌ-２抑制劑之治療方法
SG192126A1 (en) * 2011-01-25 2013-09-30 Univ Michigan Bcl-2/bcl-xl inhibitors and therapeutic methods using the same
US8940737B2 (en) 2011-10-14 2015-01-27 Abbvie Inc. Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
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
CA2861066C (en) * 2012-01-12 2024-01-02 Yale University Compounds and methods for the enhanced degradation of targeted proteins and other polypeptides by an e3 ubiquitin ligase
EP2854809B1 (en) 2012-06-01 2017-12-06 Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI) 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
CN105377289A (zh) 2013-04-21 2016-03-02 耶达研究及发展有限公司 用于下调Bcl-xL和/或Bcl-w的活性和/或量的试剂
AU2015211021B2 (en) 2014-01-28 2020-07-02 Buck Institute For Research On Aging Methods and compositions for killing senescent cells and for treating senescence-associated diseases and disorders
EP3139942B1 (en) 2014-05-05 2019-12-18 Bioventures, Llc COMPOSITIONS AND METHODS FOR INHIBITING ANTIAPOPTOTIC Bcl-2 PROTEINS AS ANTI-AGING AGENTS
US10071087B2 (en) 2014-07-22 2018-09-11 Bioventures, Llc 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
US20180002431A1 (en) 2015-01-22 2018-01-04 Bioventures, Llc FAS AND DRs ARE NOVEL MOLECULAR TARGETS OF SENESCENT CELLS
WO2016118859A1 (en) 2015-01-22 2016-07-28 Board Of Trustees Of The University Of Arkansas Compositions and methods for selectively depleting senescent cells comprising flip
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
US10730870B2 (en) * 2015-03-18 2020-08-04 Arvinas Operations, 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
CA2993118A1 (en) 2015-07-21 2017-01-26 Fundacion Universidad Catolica De Valencia San Vicente Martir Combination comprising pterostilbene for the treatment of cancer
EP3337476A4 (en) * 2015-08-19 2019-09-04 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
JP6936498B2 (ja) 2016-04-21 2021-09-15 バイオベンチャーズ・リミテッド・ライアビリティ・カンパニーＢｉｏＶｅｎｔｕｒｅｓ， ＬＬＣ 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
EP3743069B1 (en) * 2018-01-22 2025-08-06 BioVentures, LLC Bcl-2 proteins degraders for cancer treatment

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20150291562A1 (en) * 2014-04-14 2015-10-15 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Varnes, Jeffrey G., et al. "Towards the next generation of dual Bcl-2/Bcl-xL inhibitors." Bioorganic & medicinal Chemistry Letters, 2014, 24(14), pp: 3026-3033. *

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