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 (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA3018429A1 (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
EP3445765A4 (en) * 2016-04-22 2019-09-18 Dana Farber Cancer Institute, Inc. DECREASE OF CYCLINE-DEPENDENT KINASE 4/6 (CDK4 / 6) BY CONJUGATION OF CDK4 / 6 INHIBITORS WITH E3-LIGASE LIGANDS AND METHODS OF USE
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.
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
AU2019222652B2 (en) * 2018-02-13 2021-09-02 Dana-Farber Cancer Institute, Inc. Cyclin-dependent kinase degraders and methods of use
BR112020018094A2 (pt) 2018-03-08 2020-12-22 Incyte Corporation Compostos de aminopirazina diol como inibidores de pi3k-¿
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
US12539292B2 (en) 2018-04-01 2026-02-03 Arvinas Operations, Inc. BRM targeting compounds and associated methods of use
US11046658B2 (en) 2018-07-02 2021-06-29 Incyte Corporation Aminopyrazine derivatives as PI3K-γ inhibitors
JP7297053B2 (ja) 2018-08-20 2023-06-23 アルビナス・オペレーションズ・インコーポレイテッド 神経変性疾患を治療するためのｅ３ユビキチンリガーゼ結合活性を有するキメラ（ｐｒｏｔａｃ）化合物を標的とし、アルファ－シヌクレインタンパク質を標的とするタンパク質分解
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
WO2020102195A1 (en) 2018-11-13 2020-05-22 Biotheryx, Inc. Substituted isoindolinones
US20240108747A1 (en) 2019-03-21 2024-04-04 Lonza Sales Ag Extracellular vesicle conjugates and uses thereof
EP3941607A1 (en) 2019-03-21 2022-01-26 Codiak BioSciences, Inc. Process for preparing extracellular vesicles
EP3947368B1 (en) * 2019-04-04 2025-09-03 Dana-Farber Cancer Institute, Inc. Bifunctional compounds comprising a cdk2/5 ligand, a linker and a e3 ubiquitin ligase binding degron for the treatment of cancer
EP3999182A1 (en) 2019-07-17 2022-05-25 Arvinas Operations, Inc. Tau-protein targeting compounds and associated methods of use
CN114521196A (zh) * 2019-09-16 2022-05-20 诺华股份有限公司 双官能团降解剂及其使用方法
CA3154386A1 (en) 2019-10-17 2021-04-22 Michael Berlin Bifunctional molecules containing an e3 ubiquitine ligase binding moiety linked to a bcl6 targeting moiety
JP7629459B2 (ja) 2019-11-19 2025-02-13 ブリストル－マイヤーズ スクイブ カンパニー Ｈｅｌｉｏｓタンパク質の阻害剤として有用な化合物
TW202140441A (zh) 2020-03-23 2021-11-01 美商必治妥美雅史谷比公司 經取代之側氧基異吲哚啉化合物
US11739101B2 (en) * 2020-05-06 2023-08-29 Nurix Therapeutics, Inc. Bifunctional degraders of hematopoietic progenitor kinase and therapeutic uses thereof
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
WO2021237100A1 (en) 2020-05-21 2021-11-25 Codiak Biosciences, Inc. Methods of targeting extracellular vesicles to lung
WO2022047145A1 (en) 2020-08-28 2022-03-03 Arvinas Operations, Inc. Rapidly accelerating fibrosarcoma protein degrading compounds and associated methods of use
WO2022066928A2 (en) 2020-09-23 2022-03-31 Codiak Biosciences, Inc. Process for preparing extracellular vesicles
EP4320112B1 (en) 2021-04-06 2025-05-14 Bristol-Myers Squibb Company Pyridinyl substituted oxoisoindoline compounds
KR20230171979A (ko) 2021-04-16 2023-12-21 아비나스 오퍼레이션스, 인코포레이티드 Bcl6 단백질 분해의 조절제 및 관련 사용 방법
KR20240020735A (ko) 2021-05-07 2024-02-15 카이메라 쎄라퓨틱스 인코포레이티드 Cdk2 분해제 및 그 용도
WO2024054591A1 (en) 2022-09-07 2024-03-14 Arvinas Operations, Inc. Rapidly accelerated fibrosarcoma (raf) degrading compounds and associated methods of use
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

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
RU2738833C9 (ru) * 2014-04-14 2022-02-28 Арвинас, Оперэйшнз, Инк. Имидные модуляторы протеолиза и способы их применения
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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