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

    • CCHEMISTRY; METALLURGY
    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • 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

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)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicinal Preparation (AREA)
  • Plural Heterocyclic Compounds (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 (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

Also Published As

Publication number Publication date
WO2017185031A1 (en) 2017-10-26
JP6921115B2 (ja) 2021-08-18
JP2019514883A (ja) 2019-06-06
US20190092768A1 (en) 2019-03-28
AU2017254708A1 (en) 2018-10-11
CN109071552B (zh) 2022-06-03
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

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

P11 Amendment of application requested

Free format text: ST27 STATUS EVENT CODE: A-2-2-P10-P11-P100 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: AMENDMENT RECEIVED - RESPONSE TO EXAMINER'S REQUISITION

Effective date: 20240813

W00 Other event occurred

Free format text: ST27 STATUS EVENT CODE: A-2-2-W10-W00-W111 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: CORRESPONDENT DETERMINED COMPLIANT

Effective date: 20250108

P11 Amendment of application requested

Free format text: ST27 STATUS EVENT CODE: A-2-2-P10-P11-P102 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: AMENDMENT DETERMINED COMPLIANT

Effective date: 20250401

P13 Application amended

Free format text: ST27 STATUS EVENT CODE: A-2-2-P10-P13-X000 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: APPLICATION AMENDED

Effective date: 20250401

MFA Maintenance fee for application paid

Free format text: FEE DESCRIPTION TEXT: MF (APPLICATION, 8TH ANNIV.) - STANDARD

Year of fee payment: 8

U00 Fee paid

Free format text: ST27 STATUS EVENT CODE: A-2-2-U10-U00-U101 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE REQUEST RECEIVED

Effective date: 20250411

U11 Full renewal or maintenance fee paid

Free format text: ST27 STATUS EVENT CODE: A-2-2-U10-U11-U102 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE FEE PAYMENT PAID IN FULL

Effective date: 20250411

D00 Search and/or examination requested or commenced

Free format text: ST27 STATUS EVENT CODE: A-2-2-D10-D00-D149 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: EXAMINER'S INTERVIEW

Effective date: 20250603

P11 Amendment of application requested

Free format text: ST27 STATUS EVENT CODE: A-2-2-P10-P11-P101 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: AMENDMENT RECEIVED - VOLUNTARY AMENDMENT

Effective date: 20250609

W00 Other event occurred

Free format text: ST27 STATUS EVENT CODE: A-2-2-W10-W00-W111 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: CORRESPONDENT DETERMINED COMPLIANT

Effective date: 20250610