AU2017254708B2 - Degradation of cyclin-dependent kinase 4/6 (CDK4/6) by conjugation of CDK4/6 inhibitors with E3 ligase ligand and methods of use - Google Patents

Degradation of cyclin-dependent kinase 4/6 (CDK4/6) by conjugation of CDK4/6 inhibitors with E3 ligase ligand and methods of use Download PDF

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AU2017254708B2
AU2017254708B2 AU2017254708A AU2017254708A AU2017254708B2 AU 2017254708 B2 AU2017254708 B2 AU 2017254708B2 AU 2017254708 A AU2017254708 A AU 2017254708A AU 2017254708 A AU2017254708 A AU 2017254708A AU 2017254708 B2 AU2017254708 B2 AU 2017254708B2
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cancer
alkyl
cdk4
bifunctional compound
disease
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AU2017254708A1 (en
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Nathanael Gray
Baishan JIANG
Nicholas KWIATKOWSKI
Yanke LIANG
Calla M. OLSON
Eric Wang
Tinghu Zhang
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Dana Farber Cancer Institute Inc
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Dana Farber Cancer Institute Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicinal Preparation (AREA)
AU2017254708A 2016-04-22 2017-04-21 Degradation of cyclin-dependent kinase 4/6 (CDK4/6) by conjugation of CDK4/6 inhibitors with E3 ligase ligand and methods of use Active AU2017254708B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662326571P 2016-04-22 2016-04-22
US62/326,571 2016-04-22
PCT/US2017/028941 WO2017185031A1 (en) 2016-04-22 2017-04-21 Degradation of cyclin-dependent kinase 4/6 (cdk4/6) by conjugation of cdk4/6 inhibitors with e3 ligase ligand and methods of use

Publications (2)

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AU2017254708A1 AU2017254708A1 (en) 2018-10-11
AU2017254708B2 true AU2017254708B2 (en) 2021-09-16

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US (1) US10865204B2 (OSRAM)
EP (1) EP3445765A4 (OSRAM)
JP (1) JP6921115B2 (OSRAM)
CN (1) CN109071552B (OSRAM)
AU (1) AU2017254708B2 (OSRAM)
CA (1) CA3018434A1 (OSRAM)
WO (1) WO2017185031A1 (OSRAM)

Families Citing this family (54)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2017254702B2 (en) * 2016-04-22 2020-12-24 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
HUE061847T2 (hu) 2016-10-11 2023-08-28 Arvinas Operations Inc Androgén receptor célzott degradálására alkalmas vegyületek és eljárások
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.
CA3045037A1 (en) * 2016-12-08 2018-06-14 Icahn School Of Medicine At Mount Sinai Compositions and methods for treating cdk4/6-mediated cancer
US11173211B2 (en) 2016-12-23 2021-11-16 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides
CN109516989B (zh) * 2017-09-17 2021-12-31 上海美志医药科技有限公司 一类抑制并降解cdk的化合物
JP7569688B2 (ja) 2017-12-22 2024-10-18 ハイバーセル，インコーポレイテッド ホスファチジルイノシトールリン酸キナーゼ阻害剤としてのアミノピリジン誘導体
US12325725B2 (en) 2018-02-13 2025-06-10 Dana-Farber Cancer Institute, Inc. Cyclin-dependent kinase degraders and methods of use
US11174252B2 (en) 2018-02-15 2021-11-16 Nuvation Bio Inc. Heterocyclic compounds as kinase inhibitors
CA3091041A1 (en) * 2018-02-22 2019-08-29 Ichan School Of Medicine At Mount Sinai Protein arginine methyltransferase 5 (prmt5) degradation / disruption compounds and methods of use
JP2021515013A (ja) * 2018-03-06 2021-06-17 アイカーン スクール オブ メディスン アット マウント シナイ セリンスレオニンキナーゼ（ａｋｔ）分解／破壊化合物および使用方法
WO2019186343A1 (en) 2018-03-26 2019-10-03 Novartis Ag N-(3-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)benzamide derivatives
AU2019251151B2 (en) 2018-04-09 2022-07-07 Shanghaitech University Target protein degradation compounds, their anti-tumor use, their intermediates and use of intermediates
WO2019246570A1 (en) 2018-06-21 2019-12-26 Icahn School Of Medicine At Mount Sinai Wd40 repeat domain protein 5 (wdr5) degradation / disruption compounds and methods of use
JP2021529807A (ja) * 2018-07-05 2021-11-04 アイカーン スクール オブ メディスン アット マウント シナイ タンパク質チロシンキナーゼ６（ｐｔｋ６）分解／破壊化合物および使用方法
CA3106523A1 (en) * 2018-07-23 2020-01-30 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
US11707452B2 (en) 2018-08-20 2023-07-25 Arvinas Operations, Inc. Modulators of alpha-synuclein proteolysis and associated methods of use
CN113825752A (zh) * 2018-11-02 2021-12-21 威斯特解剖及生物研究所 蛋白水解靶向嵌合体
EP3880669A1 (en) 2018-11-13 2021-09-22 Biotheryx, Inc. Substituted isoindolinones
US12233356B2 (en) 2019-03-21 2025-02-25 Lonza Sales Ag Process for preparing extracellular vesicles
CN113747925B (zh) 2019-03-21 2024-10-15 隆萨销售股份公司 胞外囊泡缀合物及其用途
JP2022521825A (ja) * 2019-03-28 2022-04-12 エッサ ファーマ，インコーポレイテッド アンドロゲン受容体モジュレーター及びタンパク質分解誘導キメラリガンドとして使用するための方法
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
WO2020210337A1 (en) * 2019-04-09 2020-10-15 Dana-Farber Cancer Institute, Inc. Degradation of akt by conjugation of atp-competitive akt inhibitor gdc-0068 with e3 ligase ligands and methods of use
CA3132387A1 (en) * 2019-04-23 2020-10-29 Dana-Farber Cancer Institute, Inc. Degraders of cyclin-dependent kinase 12 (cdk12) and uses thereof
CN118908962A (zh) 2019-05-06 2024-11-08 西奈山伊坎医学院 作为hpk1的降解剂的异双功能化合物
EP3976621A4 (en) * 2019-06-03 2023-11-15 Regents of the University of Minnesota KINASE DEGRADING COMPOUNDS AND THEIR USE
TW202112767A (zh) 2019-06-17 2021-04-01 美商佩特拉製藥公司 作為磷脂酸肌醇磷酸激酶抑制劑之胺基吡啶衍生物
TWI769382B (zh) * 2019-06-21 2022-07-01 長庚大學 利博西林用於製備治療罹患磷酸二酯酶４介導疾病的患者的醫藥組合物及用途
CN110143948B (zh) * 2019-06-21 2021-05-14 上海博悦生物科技有限公司 Cdk4/6抑制剂、其药物组合物、制备方法及应用
CN114867727B (zh) 2019-07-17 2025-02-21 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
EP4045496A1 (en) 2019-10-17 2022-08-24 Arvinas Operations, Inc. Bifunctional molecules containing an e3 ubiquitine ligase binding moiety linked to a bcl6 targeting moiety
PE20230159A1 (es) 2019-12-18 2023-02-01 Novartis Ag Derivados de 3-(5-metoxi-1-oxoisoindolin-2-il)piperidin-2,6-diona y usos
CN115380026B (zh) * 2020-03-17 2023-11-07 南京明德新药研发有限公司 蛋白降解调节剂与其使用方法
CN115605488B (zh) * 2020-05-06 2024-08-09 新锐思生物制药股份有限公司 造血祖细胞激酶的双功能降解剂及其治疗用途
AU2021273458A1 (en) 2020-05-09 2022-12-01 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
US12103924B2 (en) 2020-06-01 2024-10-01 Icahn School Of Medicine At Mount Sinai Mitogen-activated protein kinase kinase (MEK) degradation compounds and methods of use
CN111909155B (zh) * 2020-08-21 2022-10-18 东莞理工学院 蛋白水解靶向嵌合体、提高其口服生物利用度的前药分子及应用
US12180193B2 (en) 2020-08-28 2024-12-31 Arvinas Operations, Inc. Accelerating fibrosarcoma protein degrading compounds and associated methods of use
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
AU2021396308A1 (en) * 2020-12-09 2023-06-22 Kymera Therapeutics, Inc. Irak degraders and uses thereof
AU2022259683A1 (en) 2021-04-16 2023-10-19 Arvinas Operations, Inc. Modulators of bcl6 proteolysis and associated methods of use
AR126052A1 (es) 2021-06-03 2023-09-06 Novartis Ag Derivados de 3-(5-oxi)-1-oxoisoindolin-2-il)piperidina-2,6-diona y sus usos
EP4416145A1 (en) * 2021-10-14 2024-08-21 Cullgen (Shanghai), Inc. Modified proteins and protein degraders
US20250186434A1 (en) * 2022-03-16 2025-06-12 Biotheryx, Inc. Sos1 protein degraders, pharmaceutical compositions thereof, and their therapeutic applications
JP2025514839A (ja) * 2022-04-25 2025-05-09 オンクオリティ ファーマシューティカルズ チャイナ リミテッド Ｃｄｋ阻害剤、医薬組成物及びその治療応用
CN115364100B (zh) * 2022-08-25 2023-08-29 杭州天玑济世生物科技有限公司 Ly2835219作为线粒体自噬诱导剂的用途
US11957759B1 (en) 2022-09-07 2024-04-16 Arvinas Operations, Inc. Rapidly accelerated fibrosarcoma (RAF) degrading compounds and associated methods of use
CN119948027A (zh) * 2022-10-21 2025-05-06 领泰生物医药(绍兴)有限公司 Sos1蛋白降解剂及其应用
WO2024183798A1 (en) * 2023-03-07 2024-09-12 Cullgen Inc. Compounds and methods of treating cancers
WO2025122895A1 (en) 2023-12-08 2025-06-12 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
WO2015160845A2 (en) * 2014-04-14 2015-10-22 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101001857B (zh) * 2002-01-22 2011-06-22 沃尼尔·朗伯有限责任公司 2-(吡啶-2-基氨基)-吡啶并[2,3-d]嘧啶-7-酮
US8685980B2 (en) * 2008-08-22 2014-04-01 Novartis Ag Pyrrolopyrimidine compounds and their uses
PA8852901A1 (es) 2008-12-22 2010-07-27 Lilly Co Eli Inhibidores de proteina cinasa
CN105294683B (zh) 2014-07-26 2018-01-23 广东东阳光药业有限公司 Cdk类小分子抑制剂的化合物及其用途
EP3191098A4 (en) 2014-09-12 2018-04-25 G1 Therapeutics, Inc. Combinations and dosing regimes to treat rb-positive tumors
WO2016040848A1 (en) 2014-09-12 2016-03-17 G1 Therapeutics, Inc. Treatment of rb-negative tumors using topoisomerase inhibitors in combination with cyclin dependent kinase 4/6 inhibitors
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
AU2017254711B2 (en) * 2016-04-22 2021-01-21 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
CA3106523A1 (en) * 2018-07-23 2020-01-30 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

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015160845A2 (en) * 2014-04-14 2015-10-22 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use

Also Published As

Publication number Publication date
AU2017254708A1 (en) 2018-10-11
US10865204B2 (en) 2020-12-15
EP3445765A4 (en) 2019-09-18
CN109071552B (zh) 2022-06-03
CN109071552A (zh) 2018-12-21
EP3445765A1 (en) 2019-02-27
CA3018434A1 (en) 2017-10-26
US20190092768A1 (en) 2019-03-28
WO2017185031A1 (en) 2017-10-26
JP6921115B2 (ja) 2021-08-18
JP2019514883A (ja) 2019-06-06

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Free format text: THE NATURE OF THE AMENDMENT IS: AMEND THE NAME OF THE INVENTOR TO READ GRAY, NATHANAEL; ZHANG, TINGHU; OLSON, CALLA M.; LIANG, YANKE; KWIATKOWSKI, NICHOLAS; WANG, ERIC AND JIANG, BAISHAN

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