JP6921115B2 - サイクリン依存性キナーゼ4/6(cdk4/6)阻害剤のe3リガーゼリガンドとのコンジュゲーションによるcdk4/6の分解および使用法 - Google Patents

サイクリン依存性キナーゼ4/6(cdk4/6)阻害剤のe3リガーゼリガンドとのコンジュゲーションによるcdk4/6の分解および使用法 Download PDF

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JP6921115B2
JP6921115B2 JP2018555281A JP2018555281A JP6921115B2 JP 6921115 B2 JP6921115 B2 JP 6921115B2 JP 2018555281 A JP2018555281 A JP 2018555281A JP 2018555281 A JP2018555281 A JP 2018555281A JP 6921115 B2 JP6921115 B2 JP 6921115B2
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ナサナエル エス. グレイ
ナサナエル エス. グレイ
ティンフー チャン
ティンフー チャン
カラー エム. オルソン
カラー エム. オルソン
ヤンケ リャン
ヤンケ リャン
ニコラス クフャトコフスキ
ニコラス クフャトコフスキ
バイシャン ジャン
バイシャン ジャン
エリック ワン
エリック ワン
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デイナ ファーバー キャンサー インスティチュート,インコーポレイテッド
デイナ ファーバー キャンサー インスティチュート,インコーポレイテッド
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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
    • C07D471/04Ortho-condensed systems
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/14Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic 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
    • C07D487/04Ortho-condensed systems

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  • Health & Medical Sciences (AREA)
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  • Immunology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicinal Preparation (AREA)
  • Plural Heterocyclic Compounds (AREA)
JP2018555281A 2016-04-22 2017-04-21 サイクリン依存性キナーゼ4/6(cdk4/6)阻害剤のe3リガーゼリガンドとのコンジュゲーションによるcdk4/6の分解および使用法 Active JP6921115B2 (ja)

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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

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Families Citing this family (58)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6927999B2 (ja) * 2016-04-22 2021-09-01 デイナ ファーバー キャンサー インスティチュート,インコーポレイテッド サイクリン依存性キナーゼ9(cdk9)阻害剤のe3リガーゼリガンドとのコンジュゲーションによるcdk9の分解および使用法
IL318681A (en) 2016-10-11 2025-03-01 Arvinas Operations Inc Compounds and methods for targeted reduction of androgen receptor
JP2019537585A (ja) * 2016-10-28 2019-12-26 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 Ezh2媒介性がんを治療するための組成物および方法
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
MX2020006587A (es) 2017-12-22 2020-12-10 Ravenna Pharmaceuticals Inc Derivados de aminopiridina como inhibidores de fosfatidilinositol fosfato cinasa.
ES3026226T3 (en) * 2018-02-13 2025-06-10 Dana Farber Cancer Inst 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
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
EP3774804A1 (en) 2018-03-26 2021-02-17 Novartis AG N-(3-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)benzamide derivatives
US12539292B2 (en) 2018-04-01 2026-02-03 Arvinas Operations, Inc. BRM targeting compounds and associated methods of use
EP3778590A4 (en) 2018-04-09 2021-12-22 ShanghaiTech University ANTI PROTEIN DEGRADATION COMPOUND, ANTITUMOR APPLICATION, INTERMEDIATE THEREOF, AND INTERMEDIATE USE
JP2021527666A (ja) * 2018-06-21 2021-10-14 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 Wd40反復ドメインタンパク質5(wdr5)分解/破壊化合物および使用の方法
CA3105121A1 (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
WO2020023480A1 (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
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
EP3873906A4 (en) * 2018-11-02 2022-07-27 The Wistar Institute of Anatomy and Biology PROTEOLYSIS-TARGETED CHIMERAS
AU2019381688A1 (en) 2018-11-13 2021-06-03 Biotheryx, Inc. Substituted isoindolinones
US20240108747A1 (en) 2019-03-21 2024-04-04 Lonza Sales Ag Extracellular vesicle conjugates and uses thereof
US12233356B2 (en) 2019-03-21 2025-02-25 Lonza Sales Ag Process for preparing extracellular vesicles
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
CA3130706A1 (en) 2019-04-04 2020-10-08 Dana-Farber Cancer Institute, Inc. Cdk2/5 degraders and uses thereof
EP3952871A4 (en) * 2019-04-09 2023-06-07 Dana-Farber Cancer Institute, Inc. AKT DEGRADATION BY CONJUGATION OF ATP COMPETITIVE AKT INHIBITOR GDC-0068 WITH E3 LIGASE LIGANDS AND METHODS OF USE
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
CN114423463B (zh) 2019-05-06 2025-09-26 西奈山伊坎医学院 作为hpk1的降解剂的异双功能化合物
US20220233702A1 (en) * 2019-06-03 2022-07-28 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
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
CN112321566B (zh) 2019-08-05 2022-06-10 上海科技大学 Egfr蛋白降解剂及其抗肿瘤应用
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
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
CA3164832A1 (en) 2019-12-18 2021-06-24 Novartis Ag 3-(5-methoxy-1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
EP4122925A4 (en) * 2020-03-17 2024-04-17 Medshine Discovery Inc. Proteolysis regulator and method for using same
CN118930560A (zh) * 2020-05-06 2024-11-12 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
TW202208345A (zh) 2020-05-09 2022-03-01 美商亞文納營運公司 雙官能性化合物的製造方法、該雙官能性化合物的超純形式、及含彼之劑型
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
US12180193B2 (en) 2020-08-28 2024-12-31 Arvinas Operations, Inc. 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
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
JP7832945B2 (ja) * 2020-12-09 2026-03-18 カイメラ セラピューティクス, インコーポレイテッド Irak分解剤およびそれらの使用
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
UY39796A (es) 2021-06-03 2023-07-31 Novartis Ag Derivados de 3–((5–oxi)–1–oxoisoindolin–2–il)piperidina–2,6–diona y sus usos
JP2024537394A (ja) * 2021-10-14 2024-10-10 クルゲン(シャンハイ),インク. 修飾タンパク質およびタンパク質分解剤
WO2023178130A1 (en) * 2022-03-16 2023-09-21 Biotheryx, Inc. Sos1 protein degraders, pharmaceutical compositions, and therapeutic applications
EP4514796A4 (en) * 2022-04-25 2026-03-18 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
EP4584258A1 (en) 2022-09-07 2025-07-16 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
CN121358732A (zh) * 2023-03-07 2026-01-16 睿跃生物科技有限公司 治疗癌症的化合物和方法
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
WO2025222132A1 (en) * 2024-04-19 2025-10-23 Foghorn Therapeutics Inc. Compounds and uses thereof
WO2025231380A1 (en) * 2024-05-02 2025-11-06 University Of Maryland, Baltimore Proteolysis targeting chimeras and methods of use thereof

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE60303009T2 (de) 2002-01-22 2006-07-13 Warner-Lambert Co. Llc 2-(pyridin-2-ylamino)-pyrido[2,3-d]pyrimidin-7-one
KR101353857B1 (ko) * 2008-08-22 2014-01-21 노파르티스 아게 Cdk 억제제로서 피롤로피리미딘 화합물
PA8852901A1 (es) * 2008-12-22 2010-07-27 Lilly Co Eli Inhibidores de proteina cinasa
JP6778114B2 (ja) * 2014-04-14 2020-10-28 アルビナス・オペレーションズ・インコーポレイテッドArvinas Operations, Inc. イミド系タンパク質分解モジュレーター及び関連する使用方法
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
WO2016040858A1 (en) 2014-09-12 2016-03-17 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
WO2016105518A1 (en) * 2014-12-23 2016-06-30 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
EP3985006A1 (en) * 2016-04-22 2022-04-20 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
WO2020023480A1 (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

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WO2017185031A1 (en) 2017-10-26
JP2019514883A (ja) 2019-06-06
US20190092768A1 (en) 2019-03-28
AU2017254708A1 (en) 2018-10-11
CN109071552B (zh) 2022-06-03
CA3018434A1 (en) 2017-10-26
US10865204B2 (en) 2020-12-15
CN109071552A (zh) 2018-12-21
AU2017254708B2 (en) 2021-09-16
EP3445765A1 (en) 2019-02-27
EP3445765A4 (en) 2019-09-18

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