CN109153675B - 细胞周期蛋白依赖性激酶9通过cdk9抑制剂与e3连接酶配体的缀合的降解及使用方法 - Google Patents

细胞周期蛋白依赖性激酶9通过cdk9抑制剂与e3连接酶配体的缀合的降解及使用方法 Download PDF

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CN109153675B
CN109153675B CN201780024826.3A CN201780024826A CN109153675B CN 109153675 B CN109153675 B CN 109153675B CN 201780024826 A CN201780024826 A CN 201780024826A CN 109153675 B CN109153675 B CN 109153675B
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cancer
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disease
compound
cdk9
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CN109153675A (zh
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N.格雷
T.张
C.M.奥尔森
Y.梁
N.奎亚特科夫斯基
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Dana Farber Cancer Institute Inc
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CN201780024826.3A 2016-04-22 2017-04-21 细胞周期蛋白依赖性激酶9通过cdk9抑制剂与e3连接酶配体的缀合的降解及使用方法 Active CN109153675B (zh)

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CN111936498B (zh) 2018-03-26 2024-04-16 诺华股份有限公司 N-(3-(7H-吡咯并[2,3-d]嘧啶-4-基)苯基)苯甲酰胺衍生物
CA3106239A1 (en) * 2018-07-27 2020-01-30 Biotheryx, Inc. Bifunctional compounds as cdk modulators
CN112912376A (zh) 2018-08-20 2021-06-04 阿尔维纳斯运营股份有限公司 用于治疗神经变性疾病的具有E3泛素连接酶结合活性并靶向α-突触核蛋白的蛋白水解靶向嵌合(PROTAC)化合物
WO2020093370A1 (zh) * 2018-11-09 2020-05-14 汪义朋 一种特异性降解tau蛋白的小分子化合物及其应用
CA3119343C (en) 2018-11-13 2024-01-16 Biotheryx, Inc. Substituted isoindolinones
US20230073777A1 (en) * 2019-02-27 2023-03-09 Cullgen (Shanghai), Inc. Cyclic-amp response element binding protein (cbp) and/or adenoviral e1a binding protein of 300 kda (p300) degradation compounds and methods of use
JP2022525924A (ja) 2019-03-21 2022-05-20 コディアック バイオサイエンシーズ， インコーポレイテッド 細胞外小胞コンジュゲート及びその使用
US12233356B2 (en) 2019-03-21 2025-02-25 Lonza Sales Ag Process for preparing extracellular vesicles
US12466809B2 (en) 2019-04-04 2025-11-11 Dana-Farber Cancer Institute, Inc. CDK2/5 degraders and uses thereof
WO2020219650A1 (en) * 2019-04-23 2020-10-29 Dana-Farber Cancer Institute, Inc. Degraders of cyclin-dependent kinase 12 (cdk12) and uses thereof
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
CN114174281B (zh) * 2019-08-05 2025-02-07 达纳-法伯癌症研究公司 细胞周期蛋白依赖性激酶7(cdk7)的降解剂及其用途
WO2021053495A1 (en) * 2019-09-16 2021-03-25 Novartis Ag Bifunctional degraders and their methods of use
CN119019369A (zh) 2019-10-17 2024-11-26 阿尔维纳斯运营股份有限公司 含有与bcl6靶向部分连接的e3泛素连接酶结合部分的双官能分子
US20230158159A1 (en) * 2020-04-24 2023-05-25 Massachusetts Institute Of Technology Chimeric degraders of cyclin-dependent kinase 9 and uses thereof
US11897930B2 (en) 2020-04-28 2024-02-13 Anwita Biosciences, Inc. Interleukin-2 polypeptides and fusion proteins thereof, and their pharmaceutical compositions and therapeutic applications
WO2021237100A1 (en) 2020-05-21 2021-11-25 Codiak Biosciences, Inc. Methods of targeting extracellular vesicles to lung
WO2022042707A1 (en) * 2020-08-27 2022-03-03 Cullgen (Shanghai) , Inc. Cyclic-amp response element binding protein (cbp) and/or adenoviral e1a binding protein of 300 kda (p300) degradation compounds and methods of use
JP2023539663A (ja) 2020-08-28 2023-09-15 アルビナス・オペレーションズ・インコーポレイテッド 急速進行性線維肉腫タンパク質分解化合物及び関連する使用方法
WO2022051616A1 (en) * 2020-09-03 2022-03-10 Board Of Regents Of The University Of Nebraska Cdk targeted heterobifunctional small molecule proteolysis targeting chimeras
US20240241020A1 (en) 2020-09-23 2024-07-18 Lonza Sales Ag Process for preparing extracellular vesicles
CN114349738B (zh) * 2020-10-14 2023-05-05 清华大学 一类靶向降解cdk2的小分子缀合物及其应用
JP2023548335A (ja) * 2020-11-05 2023-11-16 クロノス バイオ インコーポレイテッド Ｃｄｋ９活性を調節するための化合物および方法
WO2022221673A1 (en) 2021-04-16 2022-10-20 Arvinas Operations, Inc. Modulators of bcl6 proteolysis and associated methods of use
AU2022311961A1 (en) * 2021-07-16 2023-11-09 Dana-Farber Cancer Institute, Inc. Small molecule cyclin dependent kinase 4/6 (cdk4/6) and ikzf2 (helios) degraders and methods of use thereof
AU2022336575A1 (en) * 2021-09-01 2024-03-28 Xizang Haisco Pharmaceutical Co., Ltd. Compound for degradation of bcl-2 family proteins and medical application thereof
WO2023107705A1 (en) 2021-12-10 2023-06-15 Incyte Corporation Bicyclic amines as cdk12 inhibitors
WO2024054591A1 (en) 2022-09-07 2024-03-14 Arvinas Operations, Inc. Rapidly accelerated fibrosarcoma (raf) degrading compounds and associated methods of use
EP4428133A1 (en) * 2023-03-07 2024-09-11 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Bifunctional protein targeting chimeras (protacs) comprising arylidene-indolinone scaffold as dcaf11 ligand and use thereof
WO2025137613A1 (en) * 2023-12-22 2025-06-26 Ganymede Oncology, Inc. Cycloalkylene nrf2 protein degraders

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
US20150291562A1 (en) * 2014-04-14 2015-10-15 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use
CN105452244A (zh) * 2013-07-03 2016-03-30 葛兰素史克知识产权开发有限公司 作为雌激素受体抑制剂的苯并噻吩衍生物

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2007296744A1 (en) * 2006-09-11 2008-03-20 Curis, Inc. Multi-functional small molecules as anti-proliferative agents
WO2008049856A2 (en) * 2006-10-25 2008-05-02 Ingenium Pharmaceuticals Gmbh Methods of treating pain using cdk inhibitors
TW200922564A (en) * 2007-09-10 2009-06-01 Curis Inc CDK inhibitors containing a zinc binding moiety
WO2015154022A1 (en) * 2014-04-05 2015-10-08 Syros Pharmaceuticals, Inc. Inhibitors of cyclin-dependent kinase 7 (cdk7)
US10071164B2 (en) * 2014-08-11 2018-09-11 Yale University Estrogen-related receptor alpha based protac compounds and associated methods of use
WO2016105518A1 (en) * 2014-12-23 2016-06-30 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
AU2016270442C1 (en) * 2015-06-04 2022-06-02 Arvinas Operations, Inc. Imide-based modulators of proteolysis and associated methods of use
WO2017007612A1 (en) * 2015-07-07 2017-01-12 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
US11142507B2 (en) * 2015-09-09 2021-10-12 Dana-Farber Cancer Institute, Inc. Inhibitors of cyclin-dependent kinases
GB201516243D0 (en) * 2015-09-14 2015-10-28 Glaxosmithkline Ip Dev Ltd Novel compounds
WO2017079267A1 (en) * 2015-11-02 2017-05-11 Yale University Proteolysis targeting chimera compounds and methods of preparing and using same
US20200216454A1 (en) * 2015-12-30 2020-07-09 Dana-Farber Cancer Institute, Inc. Bifunctional molecules for her3 degradation and methods of use
WO2017117474A1 (en) * 2015-12-30 2017-07-06 Dana-Farber Cancer Institute, Inc. Bifunctional compounds for her3 degradation and methods of use
US10865205B2 (en) * 2016-04-22 2020-12-15 Dana-Farber Cancer Institute, Inc. Degradation of cyclin-dependent kinase 8 (CDK8) by conjugation of CDK8 inhibitors with E3 ligase ligand and methods of use
EP3445357B1 (en) * 2016-04-22 2021-05-26 Dana-Farber Cancer Institute, Inc. Bifunctional molecules for degradation of egfr and methods of use
AU2017254708B2 (en) * 2016-04-22 2021-09-16 Dana-Farber Cancer Institute, Inc. Degradation of cyclin-dependent kinase 4/6 (CDK4/6) by conjugation of CDK4/6 inhibitors with E3 ligase ligand and methods of use
WO2017197055A1 (en) * 2016-05-10 2017-11-16 C4 Therapeutics, Inc. Heterocyclic degronimers for target protein degradation
EP3454862B1 (en) * 2016-05-10 2024-09-11 C4 Therapeutics, Inc. Spirocyclic degronimers for target protein degradation
CN109641874A (zh) * 2016-05-10 2019-04-16 C4医药公司 用于靶蛋白降解的c3-碳连接的戊二酰亚胺降解决定子体
CN109790143A (zh) * 2016-05-10 2019-05-21 C4医药公司 用于靶蛋白降解的胺连接的c3-戊二酰亚胺降解决定子体
AU2017281525B2 (en) * 2016-06-23 2021-01-21 Dana-Farber Cancer Institute, Inc. Degradation of tripartite motif-containing protein 24 (TRIM24) by conjugation of TRIM24 inhibitors with E3 ligase ligand and methods of use
WO2018064589A1 (en) * 2016-09-29 2018-04-05 Dana-Farber Cancer Institute, Inc. Targeted protein degradation using a mutant e3 ubiquitin ligase

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
CN105452244A (zh) * 2013-07-03 2016-03-30 葛兰素史克知识产权开发有限公司 作为雌激素受体抑制剂的苯并噻吩衍生物
US20150291562A1 (en) * 2014-04-14 2015-10-15 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
"Modifications of the isonipecotic acid fragment of SNS-032: Analogs with improved permeability and lower efflux ratio";Junfa Fan et al.;《Bioorganic & Medicinal Chemistry Letters》;20081002;第18卷;第6236-6239页 *
"Modular PROTAC Design for the Degradation of Oncogenic BCR-ABL";Ashton C. Lai et al.;《Angew. Chem. Int. Ed.》;20161231;第55卷;第807-810页 *
"新型CDK9小分子抑制剂的设计和发现";秦立 等;《中国药理学通报》;20091030;第25卷(第10期);第1299-1303页 *

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