AU2017363252B2 - 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
AU2017363252B2
AU2017363252B2 AU2017363252A AU2017363252A AU2017363252B2 AU 2017363252 B2 AU2017363252 B2 AU 2017363252B2 AU 2017363252 A AU2017363252 A AU 2017363252A AU 2017363252 A AU2017363252 A AU 2017363252A AU 2017363252 B2 AU2017363252 B2 AU 2017363252B2
Authority
AU
Australia
Prior art keywords
alkyl
independently
absent
linker
degron
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
AU2017363252A
Other languages
English (en)
Other versions
AU2017363252A1 (en
Inventor
Dennis DOBROVOLSKY
Nathanael S. Gray
Hai-tsang HUANG
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 AU2017363252A1 publication Critical patent/AU2017363252A1/en
Application granted granted Critical
Publication of AU2017363252B2 publication Critical patent/AU2017363252B2/en
Ceased legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
    • 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
    • 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
    • C07D401/02—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 two hetero rings
    • C07D401/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • 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
    • C07D417/02—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 two hetero rings
    • C07D417/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicinal Preparation (AREA)
AU2017363252A 2016-11-22 2017-11-22 Degradation of Bruton's tyrosine kinase (BTK) by conjugation of BTK inhibitors with E3 ligase ligand and methods of use Ceased AU2017363252B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662425204P 2016-11-22 2016-11-22
US62/425,204 2016-11-22
PCT/US2017/063011 WO2018098275A1 (en) 2016-11-22 2017-11-22 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
AU2017363252A1 AU2017363252A1 (en) 2019-05-16
AU2017363252B2 true AU2017363252B2 (en) 2021-08-19

Family

ID=62195645

Family Applications (1)

Application Number Title Priority Date Filing Date
AU2017363252A Ceased AU2017363252B2 (en) 2016-11-22 2017-11-22 Degradation of Bruton's tyrosine kinase (BTK) by conjugation of BTK inhibitors with E3 ligase ligand and methods of use

Country Status (7)

Country Link
US (1) US10842878B2 (https=)
EP (1) EP3544975B1 (https=)
JP (1) JP7038712B2 (https=)
KR (1) KR102566109B1 (https=)
AU (1) AU2017363252B2 (https=)
CA (1) CA3042297A1 (https=)
WO (1) WO2018098275A1 (https=)

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11395820B2 (en) 2016-03-16 2022-07-26 H. Lee Moffitt Cancer Center And Research Institute, Inc. Small molecules against cereblon to enhance effector t cell function
PT3500299T (pt) 2016-08-19 2024-02-21 Beigene Switzerland Gmbh Combinação de zanubrutinib com um anticorpo anti-cd20 ou anti-pd-1 para utilização no tratamento do cancro
US11173211B2 (en) 2016-12-23 2021-11-16 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides
TW202515616A (zh) 2017-06-26 2025-04-16 英屬開曼群島商百濟神州有限公司 抗pd-1抗體或其抗原結合片段在製備治療用於患有肝細胞癌(hcc)之藥物的用途
CN111801334B (zh) 2017-11-29 2023-06-09 百济神州瑞士有限责任公司 使用包含btk抑制剂的组合治疗惰性或侵袭性b-细胞淋巴瘤
EP3746426A4 (en) * 2018-01-29 2021-12-29 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
US12539292B2 (en) 2018-04-01 2026-02-03 Arvinas Operations, Inc. BRM targeting compounds and associated methods of use
BR112021000395A2 (pt) 2018-07-11 2021-04-06 H. Lee Moffitt Cancer Center And Research Institute, Inc. Compostos imunomoduladores diméricos contra mecanismos baseados em cereblon
EP3841100A1 (en) 2018-08-20 2021-06-30 Arvinas Operations, Inc. Proteolysis targeting chimeric (protac) compound with e3 ubiquitin ligase binding activity and targeting alpha-synuclein protein for treating neurodegenerative diseases
JP7600123B2 (ja) 2018-10-15 2024-12-16 ニューリックス セラピューティクス，インコーポレイテッド ユビキチンプロテオソーム経路を介してｂｔｋを分解するための二官能性化合物
WO2020167518A1 (en) 2019-02-13 2020-08-20 Nurix Therapeutics, Inc. Bifunctional compounds for degrading btk via ubiquitin proteosome pathway
WO2020191369A1 (en) 2019-03-21 2020-09-24 Codiak Biosciences, Inc. Process for preparing extracellular vesicles
KR20210141554A (ko) 2019-03-21 2021-11-23 코디악 바이오사이언시즈, 인크. 세포외 소포 접합체 및 이의 용도
EP3953346A1 (en) 2019-04-09 2022-02-16 Nurix Therapeutics, Inc. 3-substituted piperidine compounds for cbl-b inhibition, and use of a cbl-b inhibitor in combination with a cancer vaccine and/or oncolytic virus
EP3969447A1 (en) 2019-05-17 2022-03-23 Nurix Therapeutics, Inc. Cyano cyclobutyl compounds for cbl-b inhibition and uses thereof
MX2021015675A (es) 2019-06-26 2022-02-03 Nurix Therapeutics Inc Compuestos de bencil-triazol sustituidos para la inhibicion de cbl-b y otros usos de los mismos.
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
WO2021018018A1 (en) * 2019-07-26 2021-02-04 Beigene, Ltd. Degradation of bruton's tyrosine kinase (btk) by conjugation of btk inidbitors with e3 ligase ligand and methods of use
EP4034141A1 (en) 2019-09-24 2022-08-03 Nurix Therapeutics, Inc. Cbl inhibitors and compositions for expansion of immune cells
CN115397821B (zh) 2019-10-17 2024-09-03 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
US20230024442A1 (en) * 2019-11-08 2023-01-26 Nurix Therapeutics, Inc. Bifunctional compounds for grading btk via ubiquitin proteosome pathway
US11820781B2 (en) 2019-12-04 2023-11-21 Nurix Therapeutics, Inc. Bifunctional compounds for degrading BTK via ubiquitin proteosome pathway
CA3162523A1 (en) 2019-12-23 2021-07-01 Hongfu LU Protein degradation agent compound preparation method and application
US20230211008A1 (en) * 2020-03-31 2023-07-06 Orum Therapeutics, Inc. Conjugates
WO2021237100A1 (en) 2020-05-21 2021-11-25 Codiak Biosciences, Inc. Methods of targeting extracellular vesicles to lung
CN113801098B (zh) 2020-06-12 2023-05-30 上海济煜医药科技有限公司 酞嗪酮类化合物及其制备方法和医药用途
CN113943293A (zh) * 2020-07-16 2022-01-18 百济神州(北京)生物科技有限公司 用于制备作为protac btk降解剂的双官能化合物的方法
JP7834721B2 (ja) 2020-08-28 2026-03-24 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
US20240241020A1 (en) 2020-09-23 2024-07-18 Lonza Sales Ag Process for preparing extracellular vesicles
JP2024504932A (ja) 2021-01-13 2024-02-02 モンテ ローザ セラピューティクス， インコーポレイテッド イソインドリノン化合物
US12016860B2 (en) 2021-04-08 2024-06-25 Nurix Therapeutics, Inc. Combination therapies with Cbl-b inhibitor compounds
CN117279910A (zh) 2021-04-16 2023-12-22 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
AU2022379494A1 (en) 2021-10-26 2024-05-30 Nurix Therapeutics, Inc. Piperidinylpyrazine-carboxamide compounds for treating and preventing cancer and for degrading btk
CA3238118A1 (en) * 2021-11-18 2023-05-25 Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Fused imide derivative
AU2022424178A1 (en) 2021-12-30 2024-07-11 Beone Medicines I Gmbh 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
CN114853735B (zh) * 2022-07-06 2022-10-21 北京鑫开元医药科技有限公司 靶向泛素化降解trk的化合物及其制备方法、组合物和用途
EP4584258A1 (en) 2022-09-07 2025-07-16 Arvinas Operations, Inc. Rapidly accelerated fibrosarcoma (raf) degrading compounds and associated methods of use
CN116283929B (zh) * 2023-01-10 2023-11-07 暨南大学 诱导egfr降解的化合物及其应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006099075A2 (en) * 2005-03-10 2006-09-21 Cgi Pharmaceuticals, Inc. Certain substituted amides, method of making, and method of use thereof
WO2009039397A2 (en) * 2007-09-20 2009-03-26 Cgi Pharmaceuticals, Inc. Substituted amides, methods of making, use thereof for the treatment of diseases such as cancer
WO2009137596A1 (en) * 2008-05-06 2009-11-12 Cgi Pharmaceuticals, Inc. Substituted amides, method of making, and use as btk inhibitors
US20160176916A1 (en) * 2014-12-23 2016-06-23 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BRPI0913879A2 (pt) 2008-07-02 2019-09-24 Hoffmann La Roche fenilpirazinonas como inibidores de quinase
JP2013104687A (ja) 2011-11-10 2013-05-30 Carna Biosciences Inc 新規な蛍光プローブ及びキナーゼ阻害剤の新規スクリーニング方法
CA2861066C (en) * 2012-01-12 2024-01-02 Yale University Compounds and methods for the enhanced degradation of targeted proteins and other polypeptides by an e3 ubiquitin ligase
AU2015247817C1 (en) * 2014-04-14 2022-02-10 Arvinas Operations, Inc. Imide-based modulators of proteolysis and associated methods of use
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
US10730870B2 (en) * 2015-03-18 2020-08-04 Arvinas Operations, Inc. Compounds and methods for the enhanced degradation of targeted proteins
GB201506871D0 (en) * 2015-04-22 2015-06-03 Glaxosmithkline Ip Dev Ltd Novel compounds

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006099075A2 (en) * 2005-03-10 2006-09-21 Cgi Pharmaceuticals, Inc. Certain substituted amides, method of making, and method of use thereof
WO2009039397A2 (en) * 2007-09-20 2009-03-26 Cgi Pharmaceuticals, Inc. Substituted amides, methods of making, use thereof for the treatment of diseases such as cancer
WO2009137596A1 (en) * 2008-05-06 2009-11-12 Cgi Pharmaceuticals, Inc. Substituted amides, method of making, and use as btk inhibitors
US20160176916A1 (en) * 2014-12-23 2016-06-23 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules

Also Published As

Publication number Publication date
EP3544975B1 (en) 2022-01-05
EP3544975A1 (en) 2019-10-02
EP3544975A4 (en) 2020-07-01
KR102566109B1 (ko) 2023-08-10
US20190262458A1 (en) 2019-08-29
JP7038712B2 (ja) 2022-03-18
WO2018098275A1 (en) 2018-05-31
KR20190077595A (ko) 2019-07-03
AU2017363252A1 (en) 2019-05-16
US10842878B2 (en) 2020-11-24
CA3042297A1 (en) 2018-05-31
JP2019535744A (ja) 2019-12-12

Similar Documents

Publication Publication Date Title
AU2017363252B2 (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
AU2019210748B2 (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
AU2017254708B2 (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
CA3089588A1 (en) Cyclin-dependent kinase inhibitors 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
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
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

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