CA3018434A1 - 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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Publication number
CA3018434A1
CA3018434A1 CA3018434A CA3018434A CA3018434A1 CA 3018434 A1 CA3018434 A1 CA 3018434A1 CA 3018434 A CA3018434 A CA 3018434A CA 3018434 A CA3018434 A CA 3018434A CA 3018434 A1 CA3018434 A1 CA 3018434A1
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Prior art keywords
cancer
alkyl
cdk4
bifunctional compound
disease
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CA3018434A
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English (en)
French (fr)
Inventor
Nathanael Gray
Tinghu Zhang
Calla M. OLSON
Yanke LIANG
Nicholas KWIATKOWSKI
Eric Wang
Baishan JIANG
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Dana Farber Cancer Institute Inc
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Dana Farber Cancer Institute Inc
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Publication of CA3018434A1 publication Critical patent/CA3018434A1/en
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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)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicinal Preparation (AREA)
CA3018434A 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 Pending CA3018434A1 (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 (1)

Publication Number Publication Date
CA3018434A1 true CA3018434A1 (en) 2017-10-26

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CA3018434A Pending CA3018434A1 (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

Country Status (7)

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

Families Citing this family (54)

* 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
HUE070289T2 (hu) 2016-10-11 2025-05-28 Arvinas Operations Inc Vegyületek és módszerek az androgénreceptor célzott lebontására
EP3532464A4 (en) * 2016-10-28 2020-07-08 Icahn School of Medicine at Mount Sinai COMPOSITIONS AND METHODS FOR THE TREATMENT OF EZH2 MEDIATION CANCER
WO2018106870A1 (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
US11667651B2 (en) 2017-12-22 2023-06-06 Hibercell, Inc. Aminopyridine derivatives as phosphatidylinositol phosphate kinase inhibitors
EP3752517B1 (en) 2018-02-13 2025-04-09 Dana-Farber Cancer Institute, Inc. Cyclin-dependent kinase degraders and methods of use
KR20200131246A (ko) 2018-02-15 2020-11-23 누베이션 바이오 인크. 키나제 억제제로서의 헤테로시클릭 화합물
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
US11472799B2 (en) 2018-03-06 2022-10-18 Icahn School Of Medicine At Mount Sinai Serine threonine kinase (AKT) degradation / disruption compounds and methods of use
JP7252973B2 (ja) 2018-03-26 2023-04-05 ノバルティス アーゲー Ｎ－（３－（７Ｈ－ピロロ［２，３－ｄ］ピリミジン－４－イル）フェニル）ベンズアミド誘導体
US12226424B2 (en) 2018-04-09 2025-02-18 Shanghaitech University Target protein degradation compounds, their anti-tumor use, their intermediates and use of intermediates
EP3810145A4 (en) * 2018-06-21 2022-06-01 Icahn School of Medicine at Mount Sinai Wd40 repeat domain protein 5 (wdr5) degradation / disruption compounds and methods of use
WO2020010204A1 (en) * 2018-07-05 2020-01-09 Icahn School Of Medicine At Mount Sinai Protein tyrosine kinase 6 (ptk6) degradation / disruption compounds and methods of use
US20210340140A1 (en) * 2018-07-23 2021-11-04 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
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
EP3873906A4 (en) * 2018-11-02 2022-07-27 The Wistar Institute of Anatomy and Biology PROTEOLYSIS-TARGETED CHIMERAS
CN113423701A (zh) 2018-11-13 2021-09-21 拜欧斯瑞克斯公司 取代的异吲哚啉酮
WO2020191369A1 (en) 2019-03-21 2020-09-24 Codiak Biosciences, Inc. Process for preparing extracellular vesicles
WO2020191377A1 (en) 2019-03-21 2020-09-24 Codiak Biosciences, Inc. Extracellular vesicle conjugates and uses thereof
WO2020198711A1 (en) * 2019-03-28 2020-10-01 Essa Pharma, Inc. Androgen receptor modulators and methods for use as proteolysis targeting chimera ligands
CA3130706A1 (en) * 2019-04-04 2020-10-08 Dana-Farber Cancer Institute, Inc. Cdk2/5 degraders and uses thereof
CA3134491A1 (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
AU2020263390B2 (en) * 2019-04-23 2026-01-08 Dana-Farber Cancer Institute, Inc. Degraders of cyclin-dependent kinase 12 (CDK12) and uses thereof
EP3965824B1 (en) 2019-05-06 2025-01-08 Icahn School of Medicine at Mount Sinai Heterobifunctional compounds as degraders of hpk1
WO2020247537A1 (en) * 2019-06-03 2020-12-10 Regents Of The University Of Minnesota Compounds that degrade kinases and uses thereof
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
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
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
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
JP7785663B2 (ja) * 2019-09-16 2025-12-15 ノバルティス アーゲー 二機能性分解誘導薬及びそれらの使用方法
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
AR120773A1 (es) 2019-12-18 2022-03-16 Novartis Ag Derivados de 3-(5-metoxi-1-oxoisoindolin-2-il)piperidin-2,6-diona como reductor de la actividad de la proteína wiz
EP4122925A4 (en) * 2020-03-17 2024-04-17 Medshine Discovery Inc. PROTEOLYSIS REGULATOR AND METHOD OF USE
TW202208381A (zh) * 2020-05-06 2022-03-01 美商紐力克斯醫療股份有限公司 造血前驅細胞激酶之雙官能降解劑及其治療用途
CN115996918A (zh) 2020-05-09 2023-04-21 阿尔维纳斯运营股份有限公司 制造双官能团化合物的方法、双官能团化合物的超纯形式以及包括所述双官能团化合物的剂型
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
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
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
EP4259128A4 (en) * 2020-12-09 2025-04-30 Kymera Therapeutics, Inc. Irak degraders and uses thereof
CR20230516A (es) 2021-04-16 2024-01-23 Arvinas Operations Inc Moduladores de la proteólisis bcl6 y métodos de uso asociados
CN117062811A (zh) 2021-06-03 2023-11-14 诺华股份有限公司 3-(1-氧代异吲哚啉-2-基)哌啶-2,6-二酮衍生物及其医疗用途
CN118451078A (zh) * 2021-10-14 2024-08-06 上海睿跃生物科技有限公司 经修饰的蛋白质和蛋白质降解剂
US20250186434A1 (en) * 2022-03-16 2025-06-12 Biotheryx, Inc. Sos1 protein degraders, pharmaceutical compositions thereof, and their therapeutic applications
EP4514796A1 (en) * 2022-04-25 2025-03-05 OnQuality Pharmaceuticals China Ltd. Cdk inhibitors, pharmaceutical compositions, and therapeutic applications
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

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GEP20063909B (en) * 2002-01-22 2006-08-25 Warner Lambert Co 2-(PYRIDIN-2-YLAMINO)-PYRIDO[2,3d] PYRIMIDIN-7-ONES
SI2331547T1 (sl) 2008-08-22 2014-11-28 Novartis Ag Pirolopirimidinske spojine kot CDK inhibitorji
PA8852901A1 (es) * 2008-12-22 2010-07-27 Lilly Co Eli Inhibidores de proteina cinasa
KR20170002446A (ko) * 2014-04-14 2017-01-06 아비나스 인코포레이티드 단백질분해의 이미드-기초된 조절인자 및 연관된 이용 방법
WO2016015605A1 (en) * 2014-07-26 2016-02-04 Sunshine Lake Pharma Co., Ltd. Compounds as cdk small-molecule inhibitors and uses thereof
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
WO2016040858A1 (en) 2014-09-12 2016-03-17 G1 Therapeutics, Inc. Combinations and dosing regimes to treat rb-positive tumors
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
CA3020543A1 (en) * 2016-04-22 2017-10-26 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
US20210340140A1 (en) * 2018-07-23 2021-11-04 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

Also Published As

Publication number Publication date
CN109071552A (zh) 2018-12-21
EP3445765A1 (en) 2019-02-27
US20190092768A1 (en) 2019-03-28
WO2017185031A1 (en) 2017-10-26
US10865204B2 (en) 2020-12-15
AU2017254708B2 (en) 2021-09-16
JP2019514883A (ja) 2019-06-06
CN109071552B (zh) 2022-06-03
JP6921115B2 (ja) 2021-08-18
EP3445765A4 (en) 2019-09-18
AU2017254708A1 (en) 2018-10-11

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