CN109311869B - 通过细胞周期蛋白-依赖性激酶8(cdk8)抑制剂与e3连接酶配体的缀合降解cdk8和使用方法 - Google Patents

通过细胞周期蛋白-依赖性激酶8(cdk8)抑制剂与e3连接酶配体的缀合降解cdk8和使用方法 Download PDF

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CN109311869B
CN109311869B CN201780024815.5A CN201780024815A CN109311869B CN 109311869 B CN109311869 B CN 109311869B CN 201780024815 A CN201780024815 A CN 201780024815A CN 109311869 B CN109311869 B CN 109311869B
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cancer
disease
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cdk8
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CN109311869A (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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CN201780024815.5A 2016-04-22 2017-04-21 通过细胞周期蛋白-依赖性激酶8(cdk8)抑制剂与e3连接酶配体的缀合降解cdk8和使用方法 Active CN109311869B (zh)

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US201662326584P 2016-04-22 2016-04-22
US62/326584 2016-04-22
PCT/US2017/028948 WO2017185034A1 (en) 2016-04-22 2017-04-21 Degradation of cyclin-dependent kinase 8 (cdk8) by conjugation of cdk8 inhibitors with e3 ligase ligand and methods of use

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Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017185023A1 (en) * 2016-04-22 2017-10-26 Dana-Farber Cancer Institute, Inc. Degradation of cyclin-dependent kinase 9 (cdk9) by conjugation of cdk9 inhibitors with e3 ligase ligand 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
KR20250044800A (ko) 2016-10-11 2025-04-01 아비나스 오퍼레이션스, 인코포레이티드 안드로겐 수용체의 표적 분해용 화합물 및 방법
EP3535265A4 (en) * 2016-11-01 2020-07-08 Arvinas, Inc. PROTACS TARGETING ON TAU PROTEIN AND RELATED METHODS FOR USE
US11173211B2 (en) 2016-12-23 2021-11-16 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides
CN108187035B (zh) * 2018-01-05 2020-12-15 杭州师范大学 E3连接酶fbw7在延缓衰老及相关疾病方面的医药用途
WO2019160890A1 (en) 2018-02-13 2019-08-22 Dana-Farber Cancer Institute, Inc. Cyclin-dependent kinase degraders and methods of use
RS63124B1 (sr) 2018-03-08 2022-05-31 Incyte Corp Aminopirazin diol jedinjenja kao pi3k-y inhibitori
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
US11046658B2 (en) 2018-07-02 2021-06-29 Incyte Corporation Aminopyrazine derivatives as PI3K-γ inhibitors
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
CN111018857B (zh) * 2018-10-09 2023-06-02 嘉兴优博生物技术有限公司 靶向蛋白酶降解平台(ted)
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
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
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
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
BR112022009514A2 (pt) 2019-11-19 2022-08-16 Bristol Myers Squibb Co Compostos úteis como inibidores de proteína helios
KR20230008176A (ko) * 2020-05-06 2023-01-13 누릭스 테라퓨틱스 인코포레이티드 조혈 전구세포 키나아제의 이작용성 분해제 및 이의 치료적 용도
EP4146642A1 (en) 2020-05-09 2023-03-15 Arvinas Operations, Inc. Methods of manufacturing a bifunctional compound, ultrapure forms of the bifunctional compound, and dosage forms comprising the same
WO2021237100A1 (en) 2020-05-21 2021-11-25 Codiak Biosciences, Inc. Methods of targeting extracellular vesicles to lung
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
US20240241020A1 (en) 2020-09-23 2024-07-18 Lonza Sales Ag Process for preparing extracellular vesicles
DK4320112T3 (da) 2021-04-06 2025-08-18 Bristol Myers Squibb Co Pyridinylsubstituerede oxoisoindolinforbindelser
WO2022221673A1 (en) 2021-04-16 2022-10-20 Arvinas Operations, Inc. Modulators of bcl6 proteolysis and associated methods of use
TW202309030A (zh) 2021-05-07 2023-03-01 美商凱麥拉醫療公司 Cdk2降解劑及其用途
WO2024054591A1 (en) 2022-09-07 2024-03-14 Arvinas Operations, Inc. Rapidly accelerated fibrosarcoma (raf) degrading compounds and associated methods of use
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

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014063054A8 (en) * 2012-10-19 2014-06-19 Dana-Farber Cancer Institute, Inc. Bone marrow on x chromosome kinase (bmx) inhibitors and uses thereof

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20250127179A (ko) * 2014-04-14 2025-08-26 아비나스 오퍼레이션스, 인코포레이티드 단백질분해의 이미드-기초된 조절인자 및 연관된 이용 방법
US10071164B2 (en) * 2014-08-11 2018-09-11 Yale University Estrogen-related receptor alpha based protac compounds and associated methods of use

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014063054A8 (en) * 2012-10-19 2014-06-19 Dana-Farber Cancer Institute, Inc. Bone marrow on x chromosome kinase (bmx) inhibitors and uses thereof

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
"Discovery of 1-(4-(4-Propionylpiperazin-1-yl) -3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl) benzo[h][1,6] naphthyridin-2(1H)-one as a Highly Potent,Selective Mammalian Target of Rapamycin (mTOR) Inhibitor for the Treatment of Cancer";Qingsong Liu;《Journal of Medicinal Chemistry》;20101231;第53卷;Table3、Figure4、Table5 *
"Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19";Aurélie Mallinger;《Journal of Medicinal Chemistry》;20160121;第59卷;Chart 1，Table 2 *
"Modular PROTAC Design for the Degradation of Oncogenic BCR-ABL";Ashton C. Lai;《Angew Chem Int Ed Engl》;20160111;第55卷(第2期);807页第1段，Figure1 *
2,8-Disubstituted-1,6-Naphthyridines and 4,6-Disubstituted-Isoquinolines with Potent, Selective Affinity for CDK8/19;Aurelie Mallinger;《Medicinal Chemistry Letters》;20160328;第7卷;全文 *
Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4;Jing Lu;《Chemistry & Biology Article》;20150618;第22卷;全文 *
Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4;Michael Zengerle;《ACS Chem. Biol》;20150602;第10卷;全文 *

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