CN109152933B - 诱导抗细胞凋亡bcl-2家族蛋白的降解的化合物及其用途 - Google Patents

诱导抗细胞凋亡bcl-2家族蛋白的降解的化合物及其用途 Download PDF

Info

Publication number
CN109152933B
CN109152933B CN201780024822.5A CN201780024822A CN109152933B CN 109152933 B CN109152933 B CN 109152933B CN 201780024822 A CN201780024822 A CN 201780024822A CN 109152933 B CN109152933 B CN 109152933B
Authority
CN
China
Prior art keywords
compound
cells
formula
compounds
mixture
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.)
Active
Application number
CN201780024822.5A
Other languages
English (en)
Chinese (zh)
Other versions
CN109152933A (zh
Inventor
郑广荣
周道洪
张翾
王营营
常建辉
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.)
BioVentures LLC
Original Assignee
BioVentures LLC
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 BioVentures LLC filed Critical BioVentures LLC
Publication of CN109152933A publication Critical patent/CN109152933A/zh
Application granted granted Critical
Publication of CN109152933B publication Critical patent/CN109152933B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Bioinformatics & Cheminformatics (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)
CN201780024822.5A 2016-04-21 2017-04-21 诱导抗细胞凋亡bcl-2家族蛋白的降解的化合物及其用途 Active CN109152933B (zh)

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

Publications (2)

Publication Number Publication Date
CN109152933A CN109152933A (zh) 2019-01-04
CN109152933B true CN109152933B (zh) 2022-12-02

Family

ID=60116391

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201780024822.5A Active CN109152933B (zh) 2016-04-21 2017-04-21 诱导抗细胞凋亡bcl-2家族蛋白的降解的化合物及其用途

Country Status (7)

Country Link
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
WO2016014625A1 (en) 2014-07-22 2016-01-28 Board Of Trustees Of The University Of Arkansas Compositions and methods for selectively depleting senescent cells
CN109152933B (zh) * 2016-04-21 2022-12-02 生物风险投资有限责任公司 诱导抗细胞凋亡bcl-2家族蛋白的降解的化合物及其用途
CN110506039A (zh) 2016-10-11 2019-11-26 阿尔维纳斯股份有限公司 用于雄激素受体靶向降解的化合物和方法
MX2019005007A (es) 2016-11-01 2019-07-18 Arvinas Inc Protac dirigidos a la proteína tau y métodos asociados de uso.
EP4467143B1 (en) 2017-07-10 2026-03-11 Celgene Corporation Method for preparing 4-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-l-oxoisoindolin-4-yl)oxy)methyl)benzyl)piperazin-l-yl)-3-fluorobenzonitrile
KR20200108301A (ko) 2018-01-10 2020-09-17 리커리엄 아이피 홀딩스, 엘엘씨 벤즈아미드 화합물
ES3041854T3 (en) * 2018-01-22 2025-11-17 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
US11026963B2 (en) * 2018-07-11 2021-06-08 Rubedo Life Sciences, Inc. Senolytic compositions and uses thereof
CN113660937A (zh) * 2019-02-08 2021-11-16 佛罗里达大学研究基金公司 治疗剂和治疗方法
AU2020310147A1 (en) * 2019-07-10 2022-01-06 Recurium Ip Holdings, Llc Bcl-2 protein inhibitors
EP3999182A1 (en) * 2019-07-17 2022-05-25 Arvinas Operations, Inc. Tau-protein targeting compounds and associated methods of use
JP7502425B2 (ja) * 2019-10-01 2024-06-18 アルヴィナス・オペレーションズ・インコーポレイテッド Ｂｒｍ標的化化合物および関連使用方法
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
US12441722B2 (en) 2020-01-15 2025-10-14 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
US20230167105A1 (en) * 2020-04-28 2023-06-01 Recurium Ip Holdings, Llc Bcl-2 protein inhibitors
CR20220630A (es) 2020-05-09 2023-01-23 Arvinas Operations Inc Métodos para fabricar un compuesto bifuncional, formas ultrapuras del compuesto bifuncional y formas de dosificación que comprenden el mismo
AU2022207648A1 (en) 2021-01-13 2023-07-27 Monte Rosa Therapeutics Ag Isoindolinone compounds
JP2024505562A (ja) 2021-02-02 2024-02-06 レス ラボラトイレス セルビエル 選択的ｂｃｌ－ｘｌ ｐｒｏｔａｃ化合物及び使用の方法
KR20240020735A (ko) 2021-05-07 2024-02-15 카이메라 쎄라퓨틱스 인코포레이티드 Cdk2 분해제 및 그 용도
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
JP2024534223A (ja) * 2021-09-01 2024-09-18 シーザン ハイスーク ファーマシューティカル カンパニー リミテッド Ｂｃｌ－２ファミリータンパク質を分解する化合物及びその医薬的な応用
US20250197387A1 (en) * 2021-09-17 2025-06-19 Kymera Therapeutics, Inc. Bcl-xl degraders and uses thereof
US20250136593A1 (en) * 2021-11-17 2025-05-01 Hitgen Inc. Degradation agent and use thereof
JP7825122B2 (ja) * 2022-01-04 2026-03-06 上海科技大学 Ｂｃｌ－２ファミリータンパク質リガンド化合物に基づいて開発したタンパク質分解剤及びそれらの応用
WO2023205802A2 (en) * 2022-04-22 2023-10-26 Sens Research Foundation Senolytic targets of senescent cells
WO2023215449A1 (en) 2022-05-06 2023-11-09 Treeline Biosciences, Inc. Tetrahydroisoquinoline heterobifunctional bcl-xl degraders
EP4519259A1 (en) 2022-05-06 2025-03-12 Treeline Biosciences, Inc. Tetrahydroisoquinoline heterobifunctional bcl-xl degraders
EP4519260A1 (en) 2022-05-06 2025-03-12 Treeline Biosciences, Inc. Tetrahydroisoquinoline heterobifunctional bcl-xdegraders
TW202402272A (zh) * 2022-07-12 2024-01-16 中國商正大天晴藥業集團股份有限公司 含有三氟甲基基團的化合物
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
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
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
TW202430522A (zh) * 2022-09-30 2024-08-01 大陸商江蘇恆瑞醫藥股份有限公司 一種用於ｂｃｌ－２蛋白靶向降解的嵌合體化合物、其製備方法及其在醫藥上的應用
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
KR20250130610A (ko) * 2022-12-06 2025-09-02 캡터 테라퓨틱스 에스.에이. 유비퀴틴 리가제 및 표적 mcl-1 단백질에 결합하는 이작용성 화합물을 사용하는 표적화된 단백질 분해
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
WO2025101575A1 (en) 2023-11-07 2025-05-15 Treeline Biosciences, Inc. Tetrahydroisoquinoline heterobifunctional bcl-x l degraders
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
TW202535872A (zh) 2023-11-07 2025-09-16 美商樹線生物科學公司 四氫異喹啉異雙功能ｂｃｌ－ｘｌ降解劑
WO2025117556A1 (en) * 2023-11-27 2025-06-05 Rubedo Life Sciences, Inc. Phosphorous containing bcl inhibitors and senolytic compounds and uses thereof
TW202535392A (zh) 2023-12-08 2025-09-16 美商亞文納營運公司 使用雄性素受體降解劑治療脊髓延髓性肌肉萎縮
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 (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103402521A (zh) * 2010-11-23 2013-11-20 Abbvie公司 使用选择性的bcl-2抑制剂的治疗方法
CN103958508A (zh) * 2011-10-14 2014-07-30 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
CN104736569A (zh) * 2012-01-12 2015-06-24 耶鲁大学 通过e3泛素连接酶增强靶蛋白质及其他多肽降解的化合物和方法
WO2015116740A1 (en) * 2014-01-28 2015-08-06 Buck Institute For Research On Aging Methods and compositions for killing senescent cells and for treating senescence-associated diseases and disorders
CN104906100A (zh) * 2009-05-26 2015-09-16 艾伯维巴哈马有限公司 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂
US20150291562A1 (en) * 2014-04-14 2015-10-15 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use
CN105246882A (zh) * 2013-01-16 2016-01-13 密执安大学评议会 BCL-2/Bcl-xL抑制剂和使用所述抑制剂的治疗方法

Family Cites Families (73)

* 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
US5270339A (en) 1991-04-05 1993-12-14 Kanagafuchi Kagaku Kogyo Kabushiki Kaisha Phenoxybenzene derivative
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
CA2338328A1 (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
WO2002097053A2 (en) 2001-05-30 2002-12-05 The Regents Of The University Of Michigan Small molecule antagonists of bcl2 family proteins
ES2276895T3 (es) 2002-05-07 2007-07-01 Institut Pasteur Cribado de peptidos qque inhiben la union de pp1c a las proteinas bcl-2, bcl-xi y 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
ES2382377T3 (es) 2003-05-30 2012-06-07 Gemin X Pharmaceuticals Canada Inc. Compuestos triheterocíclicos, composiciones, y métodos para tratar cáncer
US20050208151A1 (en) 2003-10-30 2005-09-22 Entelos, Inc. Treatment of rheumatoid arthritis with FLIP antagonists
US7973161B2 (en) 2003-11-13 2011-07-05 Abbott Laboratories Apoptosis promoters
JP2007525661A (ja) 2003-12-12 2007-09-06 セントルイス ユニバーシティー 大分子その他の分析物の検出用生物センサー
RU2361872C2 (ru) 2004-05-26 2009-07-20 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Циннамидное соединение
AU2005277223C1 (en) 2004-08-20 2009-05-21 The Regents Of The University Of Michigan Small molecule inhibitors of anti-apoptotic Bcl-2 family members and the uses thereof
PL1888550T3 (pl) 2005-05-12 2014-12-31 Abbvie Bahamas Ltd Promotory apoptozy
EP2135078B1 (en) 2007-03-09 2013-08-21 DiscoveRx Corporation Methods for identifying agents and their use for the prevention or stabilization of fibrosis
EA200901212A1 (ru) 2007-03-29 2010-04-30 Новартис Аг 3-имидазолилиндолы, предназначенные для лечения пролиферативных заболеваний
US20100310504A1 (en) 2007-09-26 2010-12-09 Lowe Scott W Methods for treating fibrosis by modulating cellular senescence
US8039668B2 (en) 2008-10-17 2011-10-18 Burnham Institute For Medical Research Naphthalene-based inhibitors of anti-apoptotic proteins
WO2009085216A2 (en) 2007-12-20 2009-07-09 Squicor Compositions and methods for detecting or elimninating senescent cells to diagnose or treat disease
US20090312373A1 (en) 2008-03-11 2009-12-17 The General Hospital Corporation Methods for the treatment of cancer using piperlongumine and piperlongumine analogs
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
NZ593536A (en) 2008-12-19 2013-07-26 Genentech Inc Quinoline derivatives and methods of use
WO2010080503A1 (en) 2008-12-19 2010-07-15 Genentech, Inc. Heterocyclic compounds and methods of use
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
US8349832B2 (en) 2009-09-02 2013-01-08 Canthera Therapeutics Compounds and compositions for treating cancer
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
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
EP2668180B1 (en) * 2011-01-25 2018-08-01 The Regents of The University of Michigan Bcl-2/bcl-xl inhibitors for use in the treatment of cancer
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
US9828344B2 (en) 2012-06-01 2017-11-28 LEIBNIZ-INSTITUT FÜR ALTERSFORSCHUNG FRITZ-LIPMANN-INSTITUT e.V. (FLI) Inhibitors of the notch signaling 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
WO2014089124A1 (en) 2012-12-03 2014-06-12 Cenexys, 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
RU2015149680A (ru) 2013-04-21 2017-05-24 Йеда Ресеарч Энд Девелопмент Ко. Лтд. Агенты для подавления активности и/или снижения количества bcl-xl и/или bcl-w
EP3139942B1 (en) 2014-05-05 2019-12-18 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
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
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
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
EP3270917A4 (en) * 2015-03-18 2018-08-08 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
AU2016295984B2 (en) 2015-07-21 2021-05-27 Fundació Investigació Hospital General Universitari De València Per A La Investigació Biomèdica I Ciències De La Salut Combination comprising pterostilbene for the treatment of cancer
US10772962B2 (en) * 2015-08-19 2020-09-15 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of bromodomain-containing proteins
WO2017101851A1 (en) 2015-12-18 2017-06-22 Unity Biotechnology, Inc. Acylsulfonamide derivatives for treating senescence-associated diseases and disorders
CN109152933B (zh) 2016-04-21 2022-12-02 生物风险投资有限责任公司 诱导抗细胞凋亡bcl-2家族蛋白的降解的化合物及其用途
US20190054097A1 (en) 2016-04-21 2019-02-21 Bioventures, Llc Compositions targeting senescent cells and the uses thereof
ES3041854T3 (en) * 2018-01-22 2025-11-17 Bioventures Llc Bcl-2 proteins degraders for cancer treatment

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104906100A (zh) * 2009-05-26 2015-09-16 艾伯维巴哈马有限公司 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂
CN103402521A (zh) * 2010-11-23 2013-11-20 Abbvie公司 使用选择性的bcl-2抑制剂的治疗方法
CN103958508A (zh) * 2011-10-14 2014-07-30 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
CN104736569A (zh) * 2012-01-12 2015-06-24 耶鲁大学 通过e3泛素连接酶增强靶蛋白质及其他多肽降解的化合物和方法
CN105246882A (zh) * 2013-01-16 2016-01-13 密执安大学评议会 BCL-2/Bcl-xL抑制剂和使用所述抑制剂的治疗方法
WO2015116740A1 (en) * 2014-01-28 2015-08-06 Buck Institute For Research On Aging Methods and compositions for killing senescent cells and for treating senescence-associated diseases and disorders
US20150291562A1 (en) * 2014-04-14 2015-10-15 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
"Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4";Michael Zengerle，et al.;《ACS Chem. Biol.》;20150602;第10卷;第1770-1777页 *
"Towards the next generation of dual Bcl-2/Bcl-xL inhibitors";Jeffrey G. Varnes，et al.;《Bioorganic & Medicinal Chemistry Letters》;20140520;第24卷;第3026-3033页 *

Also Published As

Publication number Publication date
AU2017254687B2 (en) 2021-09-30
WO2017184995A1 (en) 2017-10-26
US10807977B2 (en) 2020-10-20
EP3445452A4 (en) 2019-10-30
CA3018991A1 (en) 2017-10-26
KR20180134908A (ko) 2018-12-19
US11319316B2 (en) 2022-05-03
CN109152933A (zh) 2019-01-04
AU2017254687A1 (en) 2018-10-18
KR102447884B1 (ko) 2022-09-27
EP3445452A1 (en) 2019-02-27
JP6936498B2 (ja) 2021-09-15
US20190135801A1 (en) 2019-05-09
US20200331905A1 (en) 2020-10-22
JP2019514877A (ja) 2019-06-06
WO2020081880A1 (en) 2020-04-23

Similar Documents

Publication Publication Date Title
CN109152933B (zh) 诱导抗细胞凋亡bcl-2家族蛋白的降解的化合物及其用途
CN112105360B (zh) 用于癌症治疗的bcl-2蛋白降解剂
US20190054097A1 (en) Compositions targeting senescent cells and the uses thereof
US10905665B2 (en) Chemical modulators of signaling pathways and therapeutic use
CN105246887B (zh) 香豆素衍生物以及用于治疗过度增生性疾病的方法
JP2017522388A (ja) 老化細胞を選択的に枯渇させるための組成物及び方法
JP2017523995A (ja) Ｍｅｔａｐ−２阻害剤としてのピロリジノン誘導体
US8524897B2 (en) Crystalline oxazine derivative
JP2021519312A (ja) カルパインモジュレーター及びその治療的使用
JP6931002B2 (ja) ベンゾチアゾール両親媒性物質
CA3018991C (en) Compounds that induce degradation of anti-apoptotic bcl-2 family proteins and the uses thereof
HK1260703A1 (en) Compounds that induce degradation of anti-apoptotic bcl-2 family proteins and the uses thereof
HK1260703B (en) Compounds that induce degradation of anti-apoptotic bcl-2 family proteins and the uses thereof
JP2021501155A (ja) Ｔｇｆ−ベータ阻害剤としてのオキサジアゾール及びチアジアゾール
HK40130017A (zh) 碳酸酐酶抑制剂及其使用方法
WO2024140754A1 (zh) 一种萘酰胺类化合物、其制备方法及其应用

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
REG Reference to a national code

Ref country code: HK

Ref legal event code: DE

Ref document number: 1260703

Country of ref document: HK

GR01 Patent grant
GR01 Patent grant