CN112105360B - 用于癌症治疗的bcl-2蛋白降解剂 - Google Patents

用于癌症治疗的bcl-2蛋白降解剂 Download PDF

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CN112105360B
CN112105360B CN201980021244.9A CN201980021244A CN112105360B CN 112105360 B CN112105360 B CN 112105360B CN 201980021244 A CN201980021244 A CN 201980021244A CN 112105360 B CN112105360 B CN 112105360B
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compound
bcl
formula
cancer
compounds
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CN112105360A (zh
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郑广荣
周道洪
张翾
S·罕
Y·何
P·张
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CN201980021244.9A 2018-01-22 2019-01-22 用于癌症治疗的bcl-2蛋白降解剂 Active CN112105360B (zh)

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US201862620219P 2018-01-22 2018-01-22
US62/620219 2018-01-22
PCT/US2019/014545 WO2019144117A1 (en) 2018-01-22 2019-01-22 Bcl-2 proteins degraders for cancer treatment

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CN112105360B true CN112105360B (zh) 2024-01-30

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EP (1) EP3743069B1 (enExample)
JP (1) JP7385284B2 (enExample)
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CA (1) CA3088253A1 (enExample)
ES (1) ES3041854T3 (enExample)
WO (1) WO2019144117A1 (enExample)

Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
MX2019004950A (es) 2016-10-28 2019-09-26 Icahn School Med Mount Sinai Composiciones y metodos para tratar el cancer mediado por el potenciador del homologo zeste 2.
ES3041854T3 (en) 2018-01-22 2025-11-17 Bioventures Llc Bcl-2 proteins degraders for cancer treatment
WO2020010204A1 (en) 2018-07-05 2020-01-09 Icahn School Of Medicine At Mount Sinai Protein tyrosine kinase 6 (ptk6) degradation / disruption compounds and methods of use
CN114423463B (zh) * 2019-05-06 2025-09-26 西奈山伊坎医学院 作为hpk1的降解剂的异双功能化合物
AU2020310147A1 (en) * 2019-07-10 2022-01-06 Recurium Ip Holdings, Llc Bcl-2 protein inhibitors
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
CA3173843A1 (en) * 2020-04-28 2021-11-04 Recurium Ip Holdings, Llc Bcl-2 protein inhibitors
AU2021377235A1 (en) * 2020-11-10 2023-06-08 Dialectic Therapeutics, Inc. Small molecule formulation
WO2022140554A1 (en) * 2020-12-23 2022-06-30 Dana-Farber Cancer Institute, Inc. Small molecule degraders of phosphatidylinositol-5-phosphate 4-kinase type 2 and uses thereof
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
CN113248415B (zh) * 2021-05-26 2022-08-09 苏州正永生物医药有限公司 一种abt-737关键中间体的制备方法以及abt-737的制备方法
EP4352664A4 (en) 2021-06-11 2025-04-30 Seeqc Inc. FLUX BIASING SYSTEM AND METHOD FOR SUPERCONDUCTING QUANTUM CIRCUITS
US20240408085A1 (en) * 2021-09-01 2024-12-12 Xizang Haisco Pharmaceutical Co., Ltd. Compound for degradation of bcl-2 family proteins and medical application thereof
WO2023044046A1 (en) * 2021-09-17 2023-03-23 Kymera Therapeutics, Inc. Bcl-xl degraders and uses thereof
KR20240109245A (ko) * 2021-11-17 2024-07-10 히트젠 주식회사 분해제 및 이의 용도
CN116396288B (zh) * 2022-01-04 2026-04-03 上海科技大学 基于bcl-2家族蛋白配体化合物开发的蛋白降解剂及它们的应用
PE20250007A1 (es) 2022-05-06 2025-01-07 Treeline Biosciences Inc Degradadores bcl-xl-heterobifuncionales de tetrahidroisoquinolina
EP4519260A1 (en) 2022-05-06 2025-03-12 Treeline Biosciences, Inc. Tetrahydroisoquinoline heterobifunctional bcl-xdegraders
AU2023264537A1 (en) 2022-05-06 2024-11-14 Treeline Biosciences, Inc. Tetrahydroisoquinoline heterobifunctional bcl-xl degraders
US20260092057A1 (en) * 2022-05-12 2026-04-02 Kymera Therapeutics, Inc. Bcl-xl/bcl-2 degraders and uses thereof
CN117247374B (zh) * 2022-06-10 2026-03-17 四川科伦博泰生物医药股份有限公司 一种bcl-xl抑制剂及其制药用途
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
CN119866335A (zh) * 2022-09-30 2025-04-22 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
CN120659777A (zh) * 2022-10-03 2025-09-16 佛罗里达大学研究基金公司 募集Cereblon的Bcl-xL/Bcl-2双重降解剂
WO2024078581A1 (en) * 2022-10-12 2024-04-18 Appicine Therapeutics (Hk) Limited Selective bcl-xl protac compounds and uses thereof
CN120569222A (zh) * 2023-01-18 2025-08-29 苏州宜联生物医药有限公司 包含bcl-2家族蛋白降解剂的抗体药物偶联物及其制备方法和用途
CN121652220A (zh) * 2023-02-17 2026-03-13 正大天晴药业集团股份有限公司 含有三氟甲磺酰基的化合物
WO2024179577A1 (zh) * 2023-03-01 2024-09-06 西藏海思科制药有限公司 一种Bcl-2家族蛋白降解剂的药物组合物
CN118724870B (zh) * 2023-03-28 2026-04-28 暨南大学 蛋白降解靶向嵌合体及其应用
KR20260111020A (ko) 2023-11-07 2026-07-14 트리라인 바이오사이언시스, 인크. 테트라히드로이소퀴놀린 이종이작용성 bcl-xl 분해제
IL327973A (en) 2023-11-07 2026-06-01 Treeline Biosciences Inc Tetrahydroisoquinoline heterobifunctional bcl-xl degraders
AU2024378690A1 (en) 2023-11-07 2026-05-07 Treeline Biosciences, Inc. Tetrahydroisoquinoline heterobifunctional bcl-x l degraders

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017184995A1 (en) * 2016-04-21 2017-10-26 Bioventures, Llc Compounds that induce degradation of anti-apoptotic bcl-2 family proteins and the uses thereof
CN107614020A (zh) * 2015-03-18 2018-01-19 免疫生化公司 靶向细胞内肿瘤相关抗原的用于治疗癌症的缀合物

Family Cites Families (84)

* 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
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
ATE474568T1 (de) 2001-05-30 2010-08-15 Univ Michigan Synergistische kombination von (-) -gossypol mit docetaxel oder paclitaxel zur behandlung von krebs.
ATE345504T1 (de) 2002-05-07 2006-12-15 Pasteur Institut Screeningverfahren für peptide, die die bindung von pp1c an bcl-2, bcl-xl und bcl-w proteine inhibieren
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
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
EP1692486B1 (en) 2003-12-12 2015-10-28 Saint Louis University Biosensors for detecting macromolecules and other analytes
EP2261218B1 (en) 2004-05-26 2013-04-03 Eisai R&D Management Co., Ltd. Imidazole compound for use as an intermediate in the production of cinnamide compounds
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
US7533068B2 (en) 2004-12-23 2009-05-12 D-Wave Systems, Inc. Analog processor comprising quantum devices
ES2493466T3 (es) 2005-05-12 2014-09-11 Abbvie Bahamas Ltd. Promotores de la apoptosis
EP2135078B1 (en) 2007-03-09 2013-08-21 DiscoveRx Corporation 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
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
EP2376085B1 (en) 2008-12-19 2014-02-26 Genentech, Inc. Compounds and methods of use
KR101685718B1 (ko) 2008-12-19 2016-12-12 제넨테크, 인크. 헤테로시클릭 화합물 및 사용 방법
BRPI1016102A2 (pt) 2009-04-15 2015-09-01 Sanford Burhnham Medical Res Inst Inibidores de proteínas anti-apoptótica baseados em naftaleno
ES2546294T7 (es) 2009-05-26 2024-06-06 Abbvie Ireland Unlimited Co Agentes inductores de la apoptosis para el tratamiento de cáncer y enfermedades inmunitarias y autoinmunitarias
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
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
RU2593231C2 (ru) 2010-11-23 2016-08-10 ЭббВи Айэленд Анлимитед Компани Способы лечения с использованием селективных ингибиторов bcl-2
KR101762724B1 (ko) 2011-01-25 2017-07-28 더 리젠츠 오브 더 유니버시티 오브 미시건 Bcl-2/bcl-xl 억제제 및 이를 이용한 치료 방법
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
KR102438072B1 (ko) 2012-01-12 2022-08-31 예일 유니버시티 E3 유비퀴틴 리가아제에 의한 표적 단백질 및 다른 폴리펩티드의 증진된 분해를 위한 화합물 및 방법
WO2013178821A1 (en) 2012-06-01 2013-12-05 Leibniz-Institut für Altersforschung - 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
EP2945940B1 (en) 2013-01-16 2020-07-15 The Regents of The University of Michigan Bcl-2/bcl-xl inhibitors and their use in the treatment of cancer
BR112015026702A2 (pt) 2013-04-21 2018-02-06 Yeda Res And Developmente Co Ltd métodos de extermínio de células senescentes
US9993472B2 (en) 2014-01-28 2018-06-12 Unity Biotechnology, Inc. Treatment for osteoarthritis in a joint by administering a means for inhibiting MDM2
US10002107B2 (en) 2014-03-12 2018-06-19 D-Wave Systems Inc. Systems and methods for removing unwanted interactions in quantum devices
EP4649963A3 (en) 2014-04-14 2026-05-13 Arvinas Operations, Inc. Imide-based modulators of proteolysis and associated methods of use
CN106456699B (zh) 2014-05-05 2021-07-02 生物风险投资有限责任公司 作为抗老化剂抑制抗凋亡的Bcl-2蛋白的组合物和方法
CA2955972A1 (en) 2014-07-22 2016-01-28 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
US10552755B2 (en) 2014-08-22 2020-02-04 D-Wave Systems Inc. Systems and methods for improving the performance of a quantum processor to reduce intrinsic/control errors
US9694084B2 (en) * 2014-12-23 2017-07-04 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
US20180021323A1 (en) 2015-01-22 2018-01-25 Bioventures, Llc Flip - a selective molecular target of senescent cells
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
CN107851218A (zh) 2015-02-10 2018-03-27 D-波系统公司 用于量子处理器架构的系统、装置、物品和方法
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
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
US10296352B2 (en) 2016-06-15 2019-05-21 University Of Southern California Nested quantum annealing correction
ES3041854T3 (en) 2018-01-22 2025-11-17 Bioventures Llc Bcl-2 proteins degraders for cancer treatment

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107614020A (zh) * 2015-03-18 2018-01-19 免疫生化公司 靶向细胞内肿瘤相关抗原的用于治疗癌症的缀合物
WO2017184995A1 (en) * 2016-04-21 2017-10-26 Bioventures, Llc Compounds that induce degradation of anti-apoptotic bcl-2 family proteins and the uses thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Inhibitors of the anti-apoptotic Bcl-2 proteins: a patent review;Naval Bajwa等;《 Expert Opin . Ther . Patents 》;20121231;第22卷;第37-55页 *

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