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

Info

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
Authority
CA
Canada
Prior art keywords
cancer
alkyl
cdk4
bifunctional compound
disease
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CA3018434A
Other languages
English (en)
French (fr)
Inventor
Nathanael Gray
Tinghu Zhang
Calla M. OLSON
Yanke LIANG
Nicholas KWIATKOWSKI
Eric Wang
Baishan JIANG
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dana Farber Cancer Institute Inc
Original Assignee
Dana Farber Cancer Institute Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dana Farber Cancer Institute Inc filed Critical Dana Farber Cancer Institute Inc
Publication of CA3018434A1 publication Critical patent/CA3018434A1/en
Pending legal-status Critical Current

Links

Classifications

    • 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

Landscapes

  • 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)
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

Family

ID=60116458

Family Applications (1)

Application Number Title Priority Date Filing Date
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
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
AU2017341723B2 (en) 2016-10-11 2021-12-16 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
WO2018081530A1 (en) 2016-10-28 2018-05-03 Icahn School Of Medicine At Mount Sinai Compositions and methods for treating ezh2-mediated cancer
EP3551185A4 (en) * 2016-12-08 2021-07-14 Icahn School of Medicine at Mount Sinai COMPOSITIONS AND METHODS OF TREATMENT OF 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
BR112020012635A2 (pt) 2017-12-22 2020-12-01 Ravenna Pharmaceuticals, Inc. derivados de aminopiridina como inibidores de fosfatidilinositol fosfato quinase
AU2019222652B2 (en) * 2018-02-13 2021-09-02 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
US20210261538A1 (en) * 2018-02-22 2021-08-26 Icahn School Of Medicine At Mount Sinai Protein arginine methyltransferase 5 (prmt5) degradation / disruption compounds and methods of use
CN112154146A (zh) 2018-03-06 2020-12-29 西奈山伊坎医学院 丝氨酸苏氨酸激酶(akt)降解/破坏化合物和使用方法
EP4467549A3 (en) 2018-03-26 2025-02-19 Novartis AG Intermediates of n-(3-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)benzamide derivatives
KR102548191B1 (ko) 2018-04-09 2023-06-28 상하이테크 유니버시티 표적 단백질 분해 화합물, 이의 항종양 응용, 이의 중간체 및 중간체의 응용
CN112996518A (zh) * 2018-06-21 2021-06-18 西奈山伊坎医学院 Wd40重复结构域蛋白5(wdr5)降解/破坏化合物和使用方法
EP3817745A4 (en) * 2018-07-05 2022-04-06 Icahn School of Medicine at Mount Sinai PROTEIN TYROSINE KINASE 6 (PTK6) DEGRADATION/DISPUTED 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
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
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
US10844039B2 (en) 2018-11-13 2020-11-24 Biotheryx, Inc. Substituted isoindolinones
EP4671268A2 (en) 2019-03-21 2025-12-31 Lonza Sales AG METHOD FOR PREPARING EXTRACELLULAR VESICLES
EP3941528A1 (en) 2019-03-21 2022-01-26 Codiak BioSciences, Inc. Extracellular vesicle conjugates and uses thereof
KR20220004978A (ko) * 2019-03-28 2022-01-12 에싸 파마 아이엔씨. 단백질 분해 표적 키메라 리간드로서 사용하기 위한 안드로겐 수용체 조절제 및 방법
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
CN113645972A (zh) * 2019-04-09 2021-11-12 达纳-法伯癌症研究所有限公司 通过atp-竞争性akt抑制剂gdc-0068与e3连接酶配体的接合降解akt及使用方法
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
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
EP4031247A1 (en) * 2019-09-16 2022-07-27 Novartis AG Bifunctional degraders and their methods of use
WO2021077010A1 (en) 2019-10-17 2021-04-22 Arvinas Operations, Inc. 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
WO2021185291A1 (zh) * 2020-03-17 2021-09-23 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
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
PE20231204A1 (es) 2020-05-09 2023-08-17 Arvinas Operations Inc Metodos para fabricar un compuesto bifuncional, formas ultrapuras del compuesto bifuncional y formas de dosificacion que comprenden el mismo
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
WO2022047145A1 (en) 2020-08-28 2022-03-03 Arvinas Operations, Inc. Rapidly 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
TW202237601A (zh) * 2020-12-09 2022-10-01 美商凱麥拉醫療公司 介白素-1受體相關激酶(irak)降解物及其用途
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
KR20240013812A (ko) 2021-06-03 2024-01-30 노파르티스 아게 3-(1-옥소이소인돌린-2-일)피페리딘-2,6-디온 유도체 및 이의 의학적 용도
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
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
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
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
EA007395B3 (ru) * 2002-01-22 2018-02-28 Уорнер-Ламберт Компани Ллс 2-(ПИРИДИН-2-ИЛАМИНО)ПИРИДО[2,3-d]ПИРИМИДИН-7-ОНЫ
SI2331547T1 (sl) * 2008-08-22 2014-11-28 Novartis Ag Pirolopirimidinske spojine kot CDK inhibitorji
JO2885B1 (en) * 2008-12-22 2015-03-15 ايلي ليلي اند كومباني Protein kinase inhibitors
KR20220101015A (ko) * 2014-04-14 2022-07-18 아비나스 오퍼레이션스, 인코포레이티드 단백질분해의 이미드-기초된 조절인자 및 연관된 이용 방법
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
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
EP3191098A4 (en) 2014-09-12 2018-04-25 G1 Therapeutics, Inc. Combinations and dosing regimes to treat rb-positive tumors
EP3256470B1 (en) * 2014-12-23 2023-07-26 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
EP3445764B1 (en) * 2016-04-22 2022-06-08 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
WO2017185031A1 (en) 2017-10-26
US10865204B2 (en) 2020-12-15
AU2017254708B2 (en) 2021-09-16
CN109071552A (zh) 2018-12-21
JP6921115B2 (ja) 2021-08-18
EP3445765A4 (en) 2019-09-18
US20190092768A1 (en) 2019-03-28
JP2019514883A (ja) 2019-06-06
CN109071552B (zh) 2022-06-03
AU2017254708A1 (en) 2018-10-11
EP3445765A1 (en) 2019-02-27

Similar Documents

Publication Publication Date Title
US11247991B2 (en) Degradation of cyclin-dependent kinase 8 (CDK8) by conjugation of CDK8 inhibitors with E3 ligase ligand and methods of use
CA3018434A1 (en) Degradation of cyclin-dependent kinase 4/6 (cdk4/6) by conjugation of cdk4/6 inhibitors with e3 ligase ligand and methods of use
EP3445760B1 (en) Degradation of cyclin-dependent kinase 9 (cdk9) by conjugation of cdk9 inhibitors with e3 ligase ligand and methods of use
US10925868B2 (en) Degradation of protein kinases by conjugation of protein kinase inhibitors with E3 ligase ligand and methods of use
CA3085457C (en) Degradation of bruton's tyrosine kinase (btk) by conjugation of btk inhibitors with e3 ligase ligand and methods of use
CA3106523A1 (en) Degradation of cyclin-dependent kinase 4/6 (cdk4/6) by conjugation of cdk4/6 inhibitors with e3 ligase ligand and methods of use
CA3042301A1 (en) Degradation of protein kinases by conjugation of protein kinase inhibitors with e3 ligase ligand and methods of use
AU2017363265A1 (en) Degradation of Bruton's tyrosine kinase (BTK) by conjugation of BTK inhibitors with E3 ligase ligand and methods of use
US11279707B2 (en) NEK inhibitors and methods of use
US20230365620A1 (en) Cyclin-dependent kinase inhibitors and methods of use
AU2019222652B2 (en) Cyclin-dependent kinase degraders and methods of use
HK40072593A (en) Degradation of cyclin-dependent kinase 8 (cdk8) by conjugation of cdk8 inhibitors with e3 ligase ligand and methods of use
HK40001231A (en) Degradation of cyclin-dependent kinase 8 (cdk8) by conjugation of cdk8 inhibitors with e3 ligase ligand and methods of use
HK40001231B (en) Degradation of cyclin-dependent kinase 8 (cdk8) by conjugation of cdk8 inhibitors with e3 ligase ligand and methods of use
HK40001697B (en) Degradation of cyclin-dependent kinase 9 (cdk9) by conjugation of cdk9 inhibitors with e3 ligase ligand and methods of use
HK40001697A (en) Degradation of cyclin-dependent kinase 9 (cdk9) by conjugation of cdk9 inhibitors with e3 ligase ligand and methods of use

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20220404

EEER Examination request

Effective date: 20220404

EEER Examination request

Effective date: 20220404

EEER Examination request

Effective date: 20220404

EEER Examination request

Effective date: 20220404