AU2017254702B2 - Degradation of cyclin-dependent kinase 9 (CDK9) by conjugation of CDK9 inhibitors with E3 ligase ligand and methods of use - Google Patents

Degradation of cyclin-dependent kinase 9 (CDK9) by conjugation of CDK9 inhibitors with E3 ligase ligand and methods of use Download PDF

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AU2017254702B2
AU2017254702B2 AU2017254702A AU2017254702A AU2017254702B2 AU 2017254702 B2 AU2017254702 B2 AU 2017254702B2 AU 2017254702 A AU2017254702 A AU 2017254702A AU 2017254702 A AU2017254702 A AU 2017254702A AU 2017254702 B2 AU2017254702 B2 AU 2017254702B2
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cancer
alkyl
disease
cdk9
bifunctional compound
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AU2017254702A1 (en
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Nathanael Gray
Nicholas KWIATKOWSKI
Yanke LIANG
Calla M. OLSON
Tinghu Zhang
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Dana Farber Cancer Institute Inc
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AU2017254702A 2016-04-22 2017-04-21 Degradation of cyclin-dependent kinase 9 (CDK9) by conjugation of CDK9 inhibitors with E3 ligase ligand and methods of use Active AU2017254702B2 (en)

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US201662326581P 2016-04-22 2016-04-22
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PCT/US2017/028924 WO2017185023A1 (en) 2016-04-22 2017-04-21 Degradation of cyclin-dependent kinase 9 (cdk9) by conjugation of cdk9 inhibitors with e3 ligase ligand and methods of use

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Families Citing this family (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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US11173211B2 (en) 2016-12-23 2021-11-16 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides
US10513515B2 (en) 2017-08-25 2019-12-24 Biotheryx, Inc. Ether compounds and uses thereof
US10632209B2 (en) 2017-11-10 2020-04-28 The Regents Of The University Of Michigan ASH1L inhibitors and methods of treatment therewith
WO2019164932A1 (en) * 2018-02-20 2019-08-29 Dana-Farber Cancer Institute, Inc. Degraders of egfr and methods of use thereof
CA3087288A1 (en) * 2018-02-20 2019-08-29 Dana-Farber Cancer Institute, Inc. Inhibitors of egfr and methods of use thereof
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WO2020023782A1 (en) * 2018-07-27 2020-01-30 Biotheryx, Inc. Bifunctional compounds as cdk modulators
US11707452B2 (en) 2018-08-20 2023-07-25 Arvinas Operations, Inc. Modulators of alpha-synuclein proteolysis and associated methods of use
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
JP2022507267A (ja) 2018-11-13 2022-01-18 バイオセリックス, インコーポレイテッド 置換イソインドリノン
CN113646002A (zh) * 2019-02-27 2021-11-12 上海睿跃生物科技有限公司 环amp反应元件结合蛋白(cbp)和/或300kda腺病毒e1a结合蛋白(p300)降解化合物和使用方法
KR20210141554A (ko) 2019-03-21 2021-11-23 코디악 바이오사이언시즈, 인크. 세포외 소포 접합체 및 이의 용도
EP3941607A1 (en) 2019-03-21 2022-01-26 Codiak BioSciences, Inc. Process for preparing extracellular vesicles
ES3055186T3 (en) * 2019-04-04 2026-02-10 Dana Farber Cancer Inst Inc Bifunctional compounds comprising a cdk2/5 ligand, a linker and a e3 ubiquitin ligase binding degron for the treatment of cancer
JP2022529700A (ja) * 2019-04-23 2022-06-23 ダナ-ファーバー キャンサー インスティテュート,インコーポレイテッド サイクリン依存性キナーゼ12(cdk12)の分解剤およびその使用
EP3999182A1 (en) 2019-07-17 2022-05-25 Arvinas Operations, Inc. Tau-protein targeting compounds and associated methods of use
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
EP4031247A1 (en) * 2019-09-16 2022-07-27 Novartis AG Bifunctional degraders and their methods of use
MX2022004526A (es) 2019-10-17 2022-07-21 Arvinas Operations Inc Moléculas bifuncionales que contienen una porción de unión a la ligasa de ubiquitina e3 unida a una porción de direccionamiento a bcl6.
US20230158159A1 (en) * 2020-04-24 2023-05-25 Massachusetts Institute Of Technology Chimeric degraders of cyclin-dependent kinase 9 and uses thereof
EP4143329A4 (en) 2020-04-28 2024-10-16 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
CN116507333B (zh) * 2020-08-27 2025-05-09 上海睿跃生物科技有限公司 环amp反应元件结合蛋白(cbp)和/或300kda腺病毒e1a结合蛋白(p300)降解化合物和使用方法
WO2022047145A1 (en) 2020-08-28 2022-03-03 Arvinas Operations, Inc. Rapidly accelerating fibrosarcoma protein degrading compounds and associated methods of use
WO2022051616A1 (en) * 2020-09-03 2022-03-10 Board Of Regents Of The University Of Nebraska Cdk targeted heterobifunctional small molecule proteolysis targeting chimeras
WO2022066928A2 (en) 2020-09-23 2022-03-31 Codiak Biosciences, Inc. 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
WO2022098843A1 (en) * 2020-11-05 2022-05-12 Kronos Bio, Inc. Compounds and methods for modulating cdk9 activity
CN118388454A (zh) 2021-04-16 2024-07-26 阿尔维纳斯运营股份有限公司 Bcl6蛋白水解的调节剂和其相关使用方法
CN117396208A (zh) * 2021-07-16 2024-01-12 达纳-法伯癌症研究所公司 细胞周期蛋白依赖性激酶4/6(cdk4/6)和ikzf2(helios)的小分子降解剂及其使用方法
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
TW202329937A (zh) 2021-12-03 2023-08-01 美商英塞特公司 雙環胺ck12抑制劑
US12084453B2 (en) 2021-12-10 2024-09-10 Incyte Corporation Bicyclic amines as CDK12 inhibitors
CA3251059A1 (en) 2022-05-02 2023-11-09 The Board Of Trustees Of The Leland Stanford Junior University Compositions, systems and methods for modulating a target gene
EP4584258A1 (en) 2022-09-07 2025-07-16 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 (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20150291562A1 (en) * 2014-04-14 2015-10-15 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use

Family Cites Families (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG174772A1 (en) * 2006-09-11 2011-10-28 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
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
GB201311888D0 (en) * 2013-07-03 2013-08-14 Glaxosmithkline Ip Dev Ltd Novel compounds
EP3805218A1 (en) * 2014-04-05 2021-04-14 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
JP6815318B2 (ja) * 2014-12-23 2021-01-20 ダナ−ファーバー キャンサー インスティテュート,インコーポレイテッド 二官能性分子によって標的化タンパク質分解を誘導する方法
CA2988414C (en) * 2015-06-04 2023-09-26 Arvinas, 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
WO2017044858A2 (en) * 2015-09-09 2017-03-16 Dana-Farber Cancer Institute, Inc. Inhibitors of cyclin-dependent kinases
GB201516243D0 (en) * 2015-09-14 2015-10-28 Glaxosmithkline Ip Dev Ltd Novel compounds
BR112018008918A8 (pt) * 2015-11-02 2019-02-26 Univ Yale compostos de quimera proteólise dirigida e métodos para preparação e uso dos mesmos
WO2017117474A1 (en) * 2015-12-30 2017-07-06 Dana-Farber Cancer Institute, Inc. Bifunctional compounds for her3 degradation and methods of use
WO2017117473A1 (en) * 2015-12-30 2017-07-06 Dana-Farber Cancer Institute, Inc. Bifunctional molescules for her3 degradation and methods of use
WO2017185031A1 (en) * 2016-04-22 2017-10-26 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
WO2017185036A1 (en) * 2016-04-22 2017-10-26 Dana Farber Cancer Institute, Inc. Bifunctional molecules for degradation of egfr 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
WO2017197046A1 (en) * 2016-05-10 2017-11-16 C4 Therapeutics, Inc. C3-carbon linked glutarimide degronimers for target protein degradation
CN121974842A (zh) * 2016-05-10 2026-05-05 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
CN109562107A (zh) * 2016-05-10 2019-04-02 C4医药公司 用于靶蛋白降解的杂环降解决定子体
CN109562113A (zh) * 2016-05-10 2019-04-02 C4医药公司 用于靶蛋白降解的螺环降解决定子体
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 (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
FAN JUNFA ET AL, "Modifications of the isonipecotic acid fragment of SNS-032: Analogs with improved permeability and lower efflux ratio", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, (2008-10-02), vol. 18, no. 23, pages 6236 - 6239 *
R. E. KIERNAN ET AL, "Interaction between Cyclin T1 and SCFSKP2 Targets CDK9 for Ubiquitination and Degradation by the Proteasome", MOLECULAR AND CELLULAR BIOLOGY, (2001-12-01), vol. 21, no. 23, pages 7956 - 7970 *

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