AU2019210748B2 - Degradation of Bruton's tyrosine kinase (BTK) by conjugation of BTK inhibitors with E3 ligase ligand and methods of use - Google Patents

Degradation of Bruton's tyrosine kinase (BTK) by conjugation of BTK inhibitors with E3 ligase ligand and methods of use Download PDF

Info

Publication number
AU2019210748B2
AU2019210748B2 AU2019210748A AU2019210748A AU2019210748B2 AU 2019210748 B2 AU2019210748 B2 AU 2019210748B2 AU 2019210748 A AU2019210748 A AU 2019210748A AU 2019210748 A AU2019210748 A AU 2019210748A AU 2019210748 B2 AU2019210748 B2 AU 2019210748B2
Authority
AU
Australia
Prior art keywords
alkyl
independently
degron
linker
absent
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.)
Ceased
Application number
AU2019210748A
Other languages
English (en)
Other versions
AU2019210748A1 (en
Inventor
Dennis DOBROVOLSKY
Nathanael S. Gray
Jinhua Wang
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 AU2019210748A1 publication Critical patent/AU2019210748A1/en
Application granted granted Critical
Publication of AU2019210748B2 publication Critical patent/AU2019210748B2/en
Ceased legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05—Dipeptides
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/545—Heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/55—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • 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
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 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

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicinal Preparation (AREA)
AU2019210748A 2018-01-29 2019-01-29 Degradation of Bruton's tyrosine kinase (BTK) by conjugation of BTK inhibitors with E3 ligase ligand and methods of use Ceased AU2019210748B2 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201862623387P 2018-01-29 2018-01-29
US62/623,387 2018-01-29
US201862674946P 2018-05-22 2018-05-22
US62/674,946 2018-05-22
PCT/US2019/015505 WO2019148150A1 (en) 2018-01-29 2019-01-29 Degradation of bruton's tyrosine kinase (btk) by conjugation of btk inhibitors with e3 ligase ligand and methods of use

Publications (2)

Publication Number Publication Date
AU2019210748A1 AU2019210748A1 (en) 2020-06-18
AU2019210748B2 true AU2019210748B2 (en) 2021-08-05

Family

ID=67395727

Family Applications (1)

Application Number Title Priority Date Filing Date
AU2019210748A Ceased AU2019210748B2 (en) 2018-01-29 2019-01-29 Degradation of Bruton's tyrosine kinase (BTK) by conjugation of BTK inhibitors with E3 ligase ligand and methods of use

Country Status (6)

Country Link
US (1) US11712458B2 (enExample)
EP (1) EP3746426A4 (enExample)
JP (1) JP2021512059A (enExample)
AU (1) AU2019210748B2 (enExample)
CA (1) CA3085457C (enExample)
WO (1) WO2019148150A1 (enExample)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102861971B1 (ko) 2018-02-19 2025-09-19 광조우 루펭 파마슈티칼 컴퍼니 엘티디. Btk 및 그의 돌연변이체의 억제제
MX2021004191A (es) 2018-10-15 2021-05-27 Nurix Therapeutics Inc Compuestos bifuncionales para degradar la tirosina cinasa de bruton (btk) mediante la trayectoria de ubiquitina proteosoma.
US12582722B2 (en) 2019-02-13 2026-03-24 Nurix Therapeutics, Inc. Bifunctional compounds for degrading BTK via ubiquitin proteosome pathway
CN113490669B (zh) * 2019-03-02 2022-12-30 上海美志医药科技有限公司 一类具有降解Btk活性的化合物
WO2020252397A1 (en) * 2019-06-12 2020-12-17 Baylor College Of Medicine Small molecule proteolysis-targeting chimeras and methods of use thereof
CN114174299B (zh) * 2019-07-26 2024-10-25 百济神州有限公司 通过btk抑制剂与e3连接酶配体缀合对布鲁顿氏酪氨酸激酶(btk)的降解以及使用方法
CN110845500B (zh) * 2019-10-09 2021-05-11 清华大学 靶向btk降解化合物在治疗自身免疫系统疾病中的应用
CN110724143B (zh) * 2019-10-09 2021-03-23 清华大学 一种靶向btk蛋白降解化合物的制备及其在治疗自身免疫系统疾病与肿瘤中的应用
US20230024442A1 (en) * 2019-11-08 2023-01-26 Nurix Therapeutics, Inc. Bifunctional compounds for grading btk via ubiquitin proteosome pathway
CN112812100B (zh) * 2019-11-18 2022-04-05 四川海思科制药有限公司 一种具有降解btk激酶的化合物及其制备方法和药学上的应用
WO2021113557A1 (en) 2019-12-04 2021-06-10 Nurix Therapeutics, Inc. Bifunctional compounds for degrading btk via ubiquitin proteosome pathway
CN114478532A (zh) * 2020-10-26 2022-05-13 上海美志医药科技有限公司 靶向降解Btk的化合物及其抗肿瘤用途
CN117897388A (zh) * 2020-12-20 2024-04-16 广州麓鹏制药有限公司 Btk蛋白降解剂
US20240058457A1 (en) * 2020-12-20 2024-02-22 Newave Pharmaceutical Inc. Btk degrader
US20240139326A1 (en) * 2020-12-23 2024-05-02 Yeda Research And Development Co. Ltd. Methacrylamides protein binders and uses thereof
CN116981675A (zh) * 2020-12-31 2023-10-31 百济神州有限公司 通过布鲁顿氏酪氨酸激酶（btk）抑制剂与e3连接酶配体的缀合降解btk和使用方法
US20240216513A1 (en) * 2021-03-12 2024-07-04 Novartis Ag Fatty acid-bifunctional degrader conjugates and their methods of use
JP2024513566A (ja) * 2021-04-09 2024-03-26 ザ・ブロード・インスティテュート・インコーポレイテッド 標的基質の選択的修飾のための二官能性分子
AU2022270089A1 (en) * 2021-05-03 2023-11-16 Nurix Therapeutics, Inc. Compounds for inhibiting or degrading target proteins, compositions, comprising the same, methods of their making, and methods of their use
CN115304606B (zh) * 2021-06-21 2024-04-19 清华大学 一种同时靶向btk和gspt1蛋白的降解剂
CA3236073A1 (en) 2021-10-26 2023-05-04 Robert J. Brown Piperidinylpyrazine-carboxamide compounds for treating and preventing cancer and for degrading btk
KR20240128831A (ko) 2021-12-30 2024-08-27 베이진 스위찰랜드 게엠베하 브루톤 티로신 키나아제(btk) 억제제와 e3 리가아제 리간드의 접합에 의한 btk의 분해 및 사용 방법
WO2023125907A1 (en) * 2021-12-30 2023-07-06 Beigene, Ltd. Degradation of bruton's tyrosine kinase (btk) by conjugation of btk inhibitors with e3 ligase ligand and methods of use
JP7805983B2 (ja) 2022-03-22 2026-01-26 アッヴィ・インコーポレイテッド ブルトン型チロシンキナーゼを分解するためのピリミジン
WO2023227080A1 (zh) * 2022-05-25 2023-11-30 百极弘烨(南通)医药科技有限公司 一种protac化合物、含其的药物组合物及其制备方法和应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016169989A1 (en) * 2015-04-22 2016-10-27 Glaxosmithkline Intellectual Property Development Limited Iap e3 ligase directed proteolysis targeting chimeric molecules
WO2018098288A1 (en) * 2016-11-22 2018-05-31 Dana-Farber Cancer Institute, Inc. Degradation of bruton's tyrosine kinase (btk) by conjugation of btk inhibitors with e3 ligase ligand and methods of use
WO2018098275A1 (en) * 2016-11-22 2018-05-31 Dana-Farber Cancer Institute, Inc. Degradation of bruton's tyrosine kinase (btk) by conjugation of btk inhibitors with e3 ligase ligand and methods of use
WO2019042445A1 (zh) * 2017-09-03 2019-03-07 上海美志医药科技有限公司 一类具有抑制并降解布鲁顿酪氨酸蛋白激酶Btk活性的化合物

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CL2008002793A1 (es) * 2007-09-20 2009-09-04 Cgi Pharmaceuticals Inc Compuestos derivados de amidas sustituidas, inhibidores de la actividad de btk; composicion farmaceutica que los comprende; utiles en el tratamiento del cancer, trastornos oseos, enfermedades autoinmunes, entre otras
WO2016105518A1 (en) 2014-12-23 2016-06-30 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
US9717745B2 (en) * 2015-03-19 2017-08-01 Zhejiang DTRM Biopharma Co. Ltd. Pharmaceutical compositions and their use for treatment of cancer and autoimmune diseases
CN106146508A (zh) * 2015-03-19 2016-11-23 浙江导明医药科技有限公司 优化的联合用药及其治疗癌症和自身免疫疾病的用途
TW201701879A (zh) * 2015-04-30 2017-01-16 拜耳製藥公司 Ｉｒａｋ４抑制劑組合
AU2017254713C1 (en) 2016-04-22 2021-04-29 Dana-Farber Cancer Institute, Inc. Bifunctional molecules for degradation of EGFR and methods of use
SG11201900344YA (en) * 2016-07-15 2019-02-27 Novartis Ag Treatment and prevention of cytokine release syndrome using a chimeric antigen receptor in combination with a kinase inhibitor

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016169989A1 (en) * 2015-04-22 2016-10-27 Glaxosmithkline Intellectual Property Development Limited Iap e3 ligase directed proteolysis targeting chimeric molecules
WO2018098288A1 (en) * 2016-11-22 2018-05-31 Dana-Farber Cancer Institute, Inc. Degradation of bruton's tyrosine kinase (btk) by conjugation of btk inhibitors with e3 ligase ligand and methods of use
WO2018098275A1 (en) * 2016-11-22 2018-05-31 Dana-Farber Cancer Institute, Inc. Degradation of bruton's tyrosine kinase (btk) by conjugation of btk inhibitors with e3 ligase ligand and methods of use
WO2019042445A1 (zh) * 2017-09-03 2019-03-07 上海美志医药科技有限公司 一类具有抑制并降解布鲁顿酪氨酸蛋白激酶Btk活性的化合物

Also Published As

Publication number Publication date
JP2021512059A (ja) 2021-05-13
US11712458B2 (en) 2023-08-01
AU2019210748A1 (en) 2020-06-18
WO2019148150A1 (en) 2019-08-01
EP3746426A4 (en) 2021-12-29
EP3746426A1 (en) 2020-12-09
US20210030832A1 (en) 2021-02-04
CA3085457C (en) 2023-05-23
CA3085457A1 (en) 2019-08-01

Similar Documents

Publication Publication Date Title
AU2019210748B2 (en) Degradation of Bruton's tyrosine kinase (BTK) by conjugation of BTK inhibitors with E3 ligase ligand and methods of use
AU2017363265B2 (en) Degradation of Bruton's tyrosine kinase (BTK) by conjugation of BTK inhibitors with E3 ligase ligand and methods of use
AU2017363252B2 (en) Degradation of Bruton's tyrosine kinase (BTK) by conjugation of BTK inhibitors with E3 ligase ligand and methods of use
AU2017363257B2 (en) Degradation of protein kinases by conjugation of protein kinase inhibitors with E3 ligase ligand and methods of use
AU2017254702B2 (en) Degradation of cyclin-dependent kinase 9 (CDK9) by conjugation of CDK9 inhibitors with E3 ligase ligand and methods of use
AU2017254711B2 (en) Degradation of cyclin-dependent kinase 8 (CDK8) by conjugation of CDK8 inhibitors with E3 ligase ligand and methods of use
AU2017281525B2 (en) Degradation of tripartite motif-containing protein 24 (TRIM24) by conjugation of TRIM24 inhibitors with E3 ligase ligand and methods of use
WO2018089736A1 (en) Degradation of protein kinases by conjugation of protein kinase 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
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
AU2019222652B2 (en) Cyclin-dependent kinase degraders 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
HK40001697B (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
FGA Letters patent sealed or granted (standard patent)
MK14 Patent ceased section 143(a) (annual fees not paid) or expired