AU2017382406A1 - EGFR proteolysis targeting chimeric molecules and associated methods of use - Google Patents

EGFR proteolysis targeting chimeric molecules and associated methods of use Download PDF

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Publication number
AU2017382406A1
AU2017382406A1 AU2017382406A AU2017382406A AU2017382406A1 AU 2017382406 A1 AU2017382406 A1 AU 2017382406A1 AU 2017382406 A AU2017382406 A AU 2017382406A AU 2017382406 A AU2017382406 A AU 2017382406A AU 2017382406 A1 AU2017382406 A1 AU 2017382406A1
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Australia
Prior art keywords
alkyl
optionally substituted
substituted
aryl
group
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Abandoned
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AU2017382406A
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English (en)
Inventor
Michael Berlin
George BURSLEM
Andrew P. Crew
Craig M. Crews
Hanqing Dong
Alexey Ishchenko
Saul Jaime-Figueroa
Yimin Qian
Jing Wang
Kurt Zimmermann
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Yale University
Arvinas Operations Inc
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Yale University
Arvinas Operations Inc
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Publication of AU2017382406A1 publication Critical patent/AU2017382406A1/en
Assigned to YALE UNIVERSITY, ARVINAS OPERATIONS, INC. reassignment YALE UNIVERSITY Amend patent request/document other than specification (104) Assignors: Arvinas, Inc., YALE UNIVERSITY
Abandoned legal-status Critical Current

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    • 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
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    • 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
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    • 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
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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Medicinal Chemistry (AREA)
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  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Dermatology (AREA)
  • Neurosurgery (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Neurology (AREA)
  • Pulmonology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Biomedical Technology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
AU2017382406A 2016-12-23 2017-12-22 EGFR proteolysis targeting chimeric molecules and associated methods of use Abandoned AU2017382406A1 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201662438901P 2016-12-23 2016-12-23
US62/438,901 2016-12-23
US201762563494P 2017-09-26 2017-09-26
US62/563,494 2017-09-26
PCT/US2017/068308 WO2018119441A1 (en) 2016-12-23 2017-12-22 Egfr proteolysis targeting chimeric molecules and associated methods of use

Publications (1)

Publication Number Publication Date
AU2017382406A1 true AU2017382406A1 (en) 2019-04-18

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AU2017382406A Abandoned AU2017382406A1 (en) 2016-12-23 2017-12-22 EGFR proteolysis targeting chimeric molecules and associated methods of use

Country Status (13)

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US (3) US10994015B2 (https=)
EP (1) EP3559002A4 (https=)
JP (1) JP2020505327A (https=)
KR (1) KR20190101406A (https=)
CN (1) CN110753693A (https=)
AU (1) AU2017382406A1 (https=)
BR (1) BR112019012682A2 (https=)
CA (1) CA3047586A1 (https=)
CO (1) CO2019007892A2 (https=)
IL (1) IL267398A (https=)
MX (1) MX2019007646A (https=)
RU (1) RU2019121527A (https=)
WO (1) WO2018119441A1 (https=)

Families Citing this family (151)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180228907A1 (en) 2014-04-14 2018-08-16 Arvinas, Inc. Cereblon ligands and bifunctional compounds comprising the same
WO2016197114A1 (en) 2015-06-05 2016-12-08 Arvinas, Inc. Tank-binding kinase-1 protacs and associated methods of use
EP3319944A4 (en) 2015-07-10 2019-04-24 Arvinas, Inc. MDM2-BASED MODULATORS OF PROTEOLYSIS AND RELATED USE METHODS
US10772962B2 (en) 2015-08-19 2020-09-15 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of bromodomain-containing proteins
US20170281784A1 (en) 2016-04-05 2017-10-05 Arvinas, Inc. Protein-protein interaction inducing technology
AU2017254713C1 (en) * 2016-04-22 2021-04-29 Dana-Farber Cancer Institute, Inc. Bifunctional molecules for degradation of EGFR and methods of use
ES2990061T3 (es) 2016-05-10 2024-11-28 C4 Therapeutics Inc Degronímeros espirocíclicos para la degradación de proteínas diana
CN109790143A (zh) 2016-05-10 2019-05-21 C4医药公司 用于靶蛋白降解的胺连接的c3-戊二酰亚胺降解决定子体
EP3454856B1 (en) 2016-05-10 2024-09-11 C4 Therapeutics, Inc. Heterocyclic degronimers for target protein degradation
CN109641874A (zh) 2016-05-10 2019-04-16 C4医药公司 用于靶蛋白降解的c3-碳连接的戊二酰亚胺降解决定子体
US20180072711A1 (en) 2016-09-15 2018-03-15 Arvinas, Inc. Indole derivatives as estrogen receptor degraders
KR20190084063A (ko) 2016-10-28 2019-07-15 이칸 스쿨 오브 메디슨 엣 마운트 시나이 Ｅｚｈ２-매개성 암 치료용 조성물 및 방법
MX2019005007A (es) * 2016-11-01 2019-07-18 Arvinas Inc Protac dirigidos a la proteína tau y métodos asociados de uso.
BR112019011200B1 (pt) 2016-12-01 2021-12-28 Arvinas Operations, Inc Derivados de tetrahidronaftaleno e tetrahidroisoquinolina como degradadores do receptor de estrogênio
KR20250117470A (ko) 2016-12-23 2025-08-04 아비나스 오퍼레이션스, 인코포레이티드 급속 진행성 섬유육종 폴리펩티드의 표적화 분해를 위한 화합물 및 방법
US10806737B2 (en) 2016-12-23 2020-10-20 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of fetal liver kinase polypeptides
US11173211B2 (en) 2016-12-23 2021-11-16 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides
JP2020505327A (ja) 2016-12-23 2020-02-20 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． Ｅｇｆｒタンパク質分解標的化キメラ分子およびその関連する使用方法
US11191741B2 (en) 2016-12-24 2021-12-07 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of enhancer of zeste homolog 2 polypeptide
BR112019015312A2 (pt) 2017-01-26 2020-03-10 Arvinas Operations, Inc. Moduladores da proteólise pelo receptor de estrogênio e métodos de uso associados
IL312367A (en) 2017-01-31 2024-06-01 Arvinas Operations Inc Cereblon ligands and bifunctional compounds comprising the same
WO2018226542A1 (en) * 2017-06-09 2018-12-13 Arvinas, Inc. Modulators of proteolysis and associated methods of use
CN110769822A (zh) 2017-06-20 2020-02-07 C4医药公司 用于蛋白降解的n/o-连接的降解决定子和降解决定子体
CN109422751B (zh) * 2017-09-03 2022-04-22 上海美志医药科技有限公司 一类具有降解酪氨酸蛋白激酶jak3活性的化合物
CN118108706A (zh) 2017-09-04 2024-05-31 C4医药公司 戊二酰亚胺
WO2019043217A1 (en) 2017-09-04 2019-03-07 F. Hoffmann-La Roche Ag DIHYDROBENZIMIDAZOLONES
WO2019043208A1 (en) 2017-09-04 2019-03-07 F. Hoffmann-La Roche Ag DIHYDROQUINOLINONES
WO2019094773A1 (en) 2017-11-10 2019-05-16 The Regents Of The University Of Michigan Ash1l inhibitors and methods of treatment therewith
CN111372585A (zh) 2017-11-16 2020-07-03 C4医药公司 用于靶蛋白降解的降解剂和降解决定子
EP3710443A1 (en) 2017-11-17 2020-09-23 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of interleukin-1 receptor-associated kinase 4 polypeptides
IL315310A (en) 2017-12-26 2024-10-01 Kymera Therapeutics Inc Irak degraders and uses thereof
WO2019140380A1 (en) 2018-01-12 2019-07-18 Kymera Therapeutics, Inc. Protein degraders and uses thereof
WO2019148055A1 (en) 2018-01-26 2019-08-01 Yale University Imide-based modulators of proteolysis and methods of use
WO2019183523A1 (en) * 2018-03-23 2019-09-26 Genentech, Inc. Hetero-bifunctional degrader compounds and their use as modulators of targeted ubiquination (vhl)
EP3773576A4 (en) 2018-03-26 2021-12-29 C4 Therapeutics, Inc. Cereblon binders for the degradation of ikaros
US12539292B2 (en) 2018-04-01 2026-02-03 Arvinas Operations, Inc. BRM targeting compounds and associated methods of use
WO2019195609A2 (en) * 2018-04-04 2019-10-10 Arvinas Operations, Inc. Modulators of proteolysis and associated methods of use
WO2019196812A1 (zh) * 2018-04-09 2019-10-17 上海科技大学 蛋白降解靶向化合物、其抗肿瘤应用、其中间体及中间体应用
EP3781156A4 (en) 2018-04-16 2022-05-18 C4 Therapeutics, Inc. SPIROCYCLIC COMPOUNDS
EP3578561A1 (en) 2018-06-04 2019-12-11 F. Hoffmann-La Roche AG Spiro compounds
EP3810145A4 (en) 2018-06-21 2022-06-01 Icahn School of Medicine at Mount Sinai Wd40 repeat domain protein 5 (wdr5) degradation / disruption compounds and methods of use
WO2020010227A1 (en) 2018-07-06 2020-01-09 Kymera Therapeutics, Inc. Protein degraders and uses thereof
AR116109A1 (es) 2018-07-10 2021-03-31 Novartis Ag Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos
BR122022012697B1 (pt) 2018-07-10 2023-04-04 Novartis Ag Usos de derivados de 3-(5-hidróxi-1-oxoisoindolin-2-il)piperidina-2,6- diona, e kit
WO2020027225A1 (ja) 2018-07-31 2020-02-06 ファイメクス株式会社 複素環化合物
CN110835345A (zh) * 2018-08-17 2020-02-25 中国科学院上海药物研究所 一类细胞周期依赖性激酶的降解剂、其制备方法、药物组合物及其用途
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
US11969472B2 (en) 2018-08-22 2024-04-30 Cullgen (Shanghai), Inc. Tropomyosin receptor kinase (TRK) degradation compounds and methods of use
JP7472103B2 (ja) 2018-08-22 2024-04-22 クルゲン（シャンハイ），インク． トロポミオシン受容体キナーゼ（ｔｒｋ）分解化合物とその使用方法
WO2020051235A1 (en) 2018-09-04 2020-03-12 C4 Therapeutics, Inc. Compounds for the degradation of brd9 or mth1
CN111018857B (zh) * 2018-10-09 2023-06-02 嘉兴优博生物技术有限公司 靶向蛋白酶降解平台(ted)
CA3119773A1 (en) 2018-11-30 2020-06-04 Kymera Therapeutics, Inc. Irak degraders and uses thereof
CN120698983A (zh) 2018-12-20 2025-09-26 C4医药公司 靶向蛋白降解
CA3126141A1 (en) 2019-01-09 2020-07-16 Dana-Farber Cancer Institute, Inc. Dot1l degraders and uses thereof
EP3922632A4 (en) * 2019-02-07 2023-02-15 Korea Research Institute of Chemical Technology DEGRADATION AGENT THAT INDUCES DEGRADATION OF A TARGET EED PROTEIN, METHOD FOR ITS MANUFACTURE AND PHARMACEUTICAL COMPOSITION FOR THE PREVENTION OR TREATMENT OF DISEASES ASSOCIATED WITH EED, EZH2 OR PRC2 USING SUCH AGENT AS THE ACTIVE SUBSTANCE
CN111606883B (zh) 2019-02-25 2023-05-09 上海科技大学 基于戊二酰亚胺骨架的含硫化合物及其应用
ES2995214T3 (en) 2019-03-06 2025-02-07 C4 Therapeutics Inc Heterocyclic compounds for medical treatment
CN114269331A (zh) * 2019-03-28 2022-04-01 埃萨制药股份有限公司 雄激素受体调节剂和用作蛋白水解靶向嵌合体配体的方法
WO2020210630A1 (en) 2019-04-12 2020-10-15 C4 Therapeutics, Inc. Tricyclic degraders of ikaros and aiolos
WO2020214555A1 (en) 2019-04-16 2020-10-22 Northwestern University Bifunctional compounds comprising apcin-a and their use in the treatment of cancer
JP7503851B2 (ja) 2019-05-06 2024-06-21 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 Ｈｐｋ１の分解剤としてのヘテロ二官能性化合物
CN110204532B (zh) * 2019-05-15 2022-03-08 浙江工业大学 一种靶向egfr蛋白降解的化合物及其制备方法和应用
US12377080B2 (en) 2019-06-21 2025-08-05 Dana-Farber Cancer Institute, Inc. Allosteric EGFR inhibitors and methods of use thereof
PH12022500002A1 (en) 2019-06-28 2023-04-03 Kymera Therapeutics Inc Irak degraders and uses thereof
WO2021011868A1 (en) 2019-07-17 2021-01-21 Kymera Therapeutics, Inc. Irak degraders and uses thereof
EP3999182A1 (en) 2019-07-17 2022-05-25 Arvinas Operations, Inc. Tau-protein targeting compounds and associated methods of use
WO2021023233A1 (zh) * 2019-08-05 2021-02-11 上海科技大学 Egfr蛋白降解剂及其抗肿瘤应用
CN114286678A (zh) * 2019-08-23 2022-04-05 北京泰德制药股份有限公司 抑制并诱导降解egfr和alk的化合物
KR20220054347A (ko) 2019-08-26 2022-05-02 아비나스 오퍼레이션스, 인코포레이티드 에스트로겐 수용체 분해제로서의 테트라히드로나프탈렌 유도체로 유방암을 치료하는 방법
CA3154386A1 (en) 2019-10-17 2021-04-22 Michael Berlin Bifunctional molecules containing an e3 ubiquitine ligase binding moiety linked to a bcl6 targeting moiety
AU2020383423A1 (en) 2019-11-11 2022-06-23 Dana-Farber Cancer Institute, Inc. Allosteric EGFR inhibitors and methods of use thereof
CN114728071B (zh) * 2019-11-13 2024-12-06 新旭生技股份有限公司 用于降解tau蛋白聚集体的化合物及其用途
JP7629459B2 (ja) 2019-11-19 2025-02-13 ブリストル－マイヤーズ スクイブ カンパニー Ｈｅｌｉｏｓタンパク質の阻害剤として有用な化合物
WO2021119159A1 (en) 2019-12-10 2021-06-17 Kymera Therapeutics, Inc. Irak degraders and uses thereof
EP4079735B1 (en) * 2019-12-16 2025-08-06 Beijing Tide Pharmaceutical Co., Ltd. Macrocyclic compounds for inhibiting and inducing degradation of egfr kinase in the treatment of cancer
KR20220145325A (ko) 2019-12-17 2022-10-28 카이메라 쎄라퓨틱스 인코포레이티드 Irak 분해제 및 이의 용도
PH12022551482A1 (en) 2019-12-18 2023-11-29 Novartis Ag 3-(5-methoxy-1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
AU2020405129A1 (en) 2019-12-19 2022-06-23 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
KR20220119415A (ko) 2019-12-20 2022-08-29 씨4 테라퓨틱스, 인코포레이티드 Egfr 분해를 위한 이소인돌리논 및 인다졸 화합물
WO2023205701A1 (en) 2022-04-20 2023-10-26 Kumquat Biosciences Inc. Macrocyclic heterocycles and uses thereof
EP4110772A4 (en) 2020-02-26 2024-04-03 Cullgen (Shanghai), Inc. TROPOMYOSIN RECEPTOR KINASE (TRK) DEGRADATION COMPOUNDS AND METHODS OF USE
TW202146412A (zh) 2020-03-05 2021-12-16 美商Ｃ４醫藥公司 用於標靶降解brd9之化合物
CN113354622B (zh) * 2020-03-06 2022-11-01 沈阳药科大学 对苯二胺类lsd1抑制剂及其制备方法
TW202140441A (zh) 2020-03-23 2021-11-01 美商必治妥美雅史谷比公司 經取代之側氧基異吲哚啉化合物
CN113509557A (zh) * 2020-04-09 2021-10-19 嘉兴优博生物技术有限公司 靶向蛋白酶降解平台(ted)
KR20230018431A (ko) * 2020-05-28 2023-02-07 브리스톨-마이어스 스큅 컴퍼니 갈렉틴-3 억제제
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
TW202210483A (zh) 2020-06-03 2022-03-16 美商凱麥拉醫療公司 Irak降解劑之結晶型
JP2023530030A (ja) 2020-06-19 2023-07-12 シーフォー セラピューティクス， インコーポレイテッド Ｂｒａｆ分解剤
CN117327059A (zh) * 2020-07-08 2024-01-02 北京泰德制药股份有限公司 抑制并诱导蛋白降解的化合物
IL300397A (en) 2020-08-05 2023-04-01 C4 Therapeutics Inc Compounds for targeted knockdown of RET
CN114057770B (zh) * 2020-08-06 2023-05-02 成都先导药物开发股份有限公司 靶向egfr蛋白降解的双功能化合物
WO2022047145A1 (en) 2020-08-28 2022-03-03 Arvinas Operations, Inc. Rapidly accelerating fibrosarcoma protein degrading compounds and associated methods of use
CN116490184B (zh) * 2020-09-11 2025-06-20 J2H生物科技有限公司 用于抑制egfr突变癌症的化合物及其药物用途
CN116368152A (zh) * 2020-09-13 2023-06-30 山东博安生物技术股份有限公司 通过受体tac技术的膜结合蛋白的下调
WO2022056368A1 (en) 2020-09-14 2022-03-17 Arvinas Operations, Inc. Crystalline forms of a compound for the targeted degradation of estrogen receptor
CN114621231B (zh) * 2020-12-14 2025-09-12 杭州中美华东制药有限公司 一种靶向降解/抑制活性的嵌合化合物及其制备方法和用途
CN112661707B (zh) * 2020-12-25 2022-11-08 扬子江药业集团有限公司 达可替尼的制备方法
CN112608302B (zh) * 2020-12-28 2022-05-24 郑州大学第一附属医院 低氧还原激活靶向泛素化降解egfr蛋白的喹唑啉类衍生物及其应用
CN116867758A (zh) 2020-12-30 2023-10-10 凯麦拉医疗公司 Irak降解剂和其用途
AU2022207648A1 (en) 2021-01-13 2023-07-27 Monte Rosa Therapeutics Ag Isoindolinone compounds
CN112939965B (zh) * 2021-02-08 2023-02-24 沈阳药科大学 同时诱导egfr和parp蛋白降解的化合物及制备方法和应用
CN116847848A (zh) 2021-02-10 2023-10-03 百济神州有限公司 Egfr降解剂和使用方法
US12171768B2 (en) 2021-02-15 2024-12-24 Kymera Therapeutics, Inc. IRAK4 degraders and uses thereof
CN116867494A (zh) 2021-02-15 2023-10-10 凯麦拉医疗公司 Irak4降解剂和其用途
CN113004251B (zh) * 2021-03-05 2022-09-27 郑州大学第一附属医院 含2-硝基咪唑的喹唑啉类衍生物及其应用
EP4320112B1 (en) 2021-04-06 2025-05-14 Bristol-Myers Squibb Company Pyridinyl substituted oxoisoindoline compounds
KR20230171979A (ko) 2021-04-16 2023-12-21 아비나스 오퍼레이션스, 인코포레이티드 Bcl6 단백질 분해의 조절제 및 관련 사용 방법
CN115232108B (zh) * 2021-04-23 2025-04-18 领泰生物医药(绍兴)有限公司 Sos1降解剂及其制备方法和应用
EP4330251A4 (en) * 2021-04-30 2025-03-05 BeiGene Switzerland GmbH EGFR DEGRADING AGENTS AND METHODS OF USE THEREOF
TW202309039A (zh) 2021-05-05 2023-03-01 美商百健Ｍａ公司 用於靶向布魯頓氏酪胺酸激酶降解之化合物
WO2022251588A1 (en) * 2021-05-27 2022-12-01 Halda Therapeutics Opco, Inc. Heterobifunctional compounds and methods of treating disease
WO2022254362A1 (en) 2021-06-03 2022-12-08 Novartis Ag 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and medical uses thereof
KR20220170766A (ko) * 2021-06-22 2022-12-30 주식회사 엘지화학 단백질 키나아제 억제제로서의 신규한 화합물
BR112023025403A2 (pt) 2021-06-25 2024-02-20 Korea Res Inst Chemical Tech Composto heterocíclico bifuncional tendo função de degradação de btk por meio da via ubiquitina proteassoma e uso do mesmo
TW202317561A (zh) * 2021-07-01 2023-05-01 美商羅曼德生物治療公司 作為治療劑的具有１ｈ—吡唑并［４，３—ｃ］吡啶—６—胺基的化合物
WO2023283130A1 (en) 2021-07-04 2023-01-12 Newave Pharmaceutical Inc. Isoquinoline derivatives as mutant egfr modulators and uses thereof
US20250018046A1 (en) 2021-07-07 2025-01-16 Biogen Ma Inc Compounds for targeting degradation of irak4 proteins
EP4367113A1 (en) 2021-07-07 2024-05-15 Biogen MA Inc. Compounds for targeting degradation of irak4 proteins
CA3226162A1 (en) 2021-07-09 2023-01-12 Plexium, Inc. Aryl compounds and pharmaceutical compositions that modulate ikzf2
CN113636931B (zh) * 2021-08-05 2024-02-13 康龙化成(宁波)科技发展有限公司 基因编码化合物库起始头片段化合物及其在基因编码化合物库合成上的应用
CN113683491A (zh) * 2021-09-01 2021-11-23 王传良 一种4-(2-溴乙基)苯酚的制备方法
CN115109047B (zh) * 2021-09-08 2024-02-20 中国科学院化学研究所 一种基于protac设计的铁死亡诱导剂
CA3236265A1 (en) 2021-10-29 2023-05-04 William Leong Irak4 degraders and synthesis thereof
CN116135852B (zh) * 2021-11-17 2025-09-05 浙江同源康医药股份有限公司 用于egfr蛋白降解的化合物及其用途
CN114349739A (zh) * 2021-12-14 2022-04-15 杭州医学院 一种降解微管蛋白的偶氮类化合物及其合成方法和应用
CA3243560A1 (en) 2022-01-31 2023-08-03 Kymera Therapeutics, Inc. Iraqi Degradation Agents and Their Uses
CN115160311B (zh) * 2022-05-26 2024-03-15 北京康辰药业股份有限公司 一种用于egfr降解的双功能化合物及其应用
CN115109055B (zh) * 2022-05-26 2023-11-28 北京康辰药业股份有限公司 一种用于egfr降解的双功能化合物及其应用
CA3249074A1 (en) 2022-06-06 2023-12-14 C4 Therapeutics, Inc. BICYCLIC SUBSTITUTION GLUTARIMIDE CEREBLON BINDERS
CN115073439B (zh) * 2022-07-22 2023-10-20 徐州医科大学 一种嘧啶类化合物及其医药用途
CN115650975B (zh) * 2022-08-23 2024-07-02 四川大学华西医院 一种靶向降解人表皮生长因子受体2的蛋白降解靶向嵌合体化合物及其应用
WO2024054591A1 (en) 2022-09-07 2024-03-14 Arvinas Operations, Inc. Rapidly accelerated fibrosarcoma (raf) degrading compounds and associated methods of use
WO2024073507A1 (en) 2022-09-28 2024-04-04 Theseus Pharmaceuticals, Inc. Macrocyclic compounds and uses thereof
US20240246963A1 (en) * 2022-12-08 2024-07-25 Risen (Suzhou) Pharma Tech Co., Ltd. Bifunctional compounds and pharmaceutical uses thereof
US12448399B2 (en) 2023-01-26 2025-10-21 Arvinas Operations, Inc. Cereblon-based KRAS degrading PROTACs and uses related thereto
WO2024206163A1 (en) * 2023-03-24 2024-10-03 The Children's Hospital Of Philadelphia Large-scale induction of protein-protein interactions to discover novel effector proteins for proximity-based therapeutics
PE20252789A1 (es) 2023-05-24 2025-12-22 Kumquat Biosciences Inc Compuestos heterociclicos y usos de estos
EP4720071A1 (en) 2023-05-31 2026-04-08 Beone Medicines I GmbH Compounds for the degradation of egfr kinase
CN121263417A (zh) 2023-06-30 2026-01-02 金橘生物科技公司 取代的稠合三环胺化合物及其作为ras抑制剂的用途
CN116693505B (zh) * 2023-07-28 2023-10-27 中国药科大学 一种靶向降解egfr蛋白的化合物及其制法和应用
WO2025063888A1 (en) 2023-09-19 2025-03-27 Kancure Pte. Ltd. Survivin-targeted compounds
KR20250044979A (ko) 2023-09-25 2025-04-01 주식회사 메디아크 프로탁(Protac)이 탑재된 금속-유기 골격체(Metal-Organic Framework) 입자를 포함하는 약물 전달 시스템 및 이를 포함하는 약학 조성물
TW202530189A (zh) 2023-09-29 2025-08-01 日商第一三共股份有限公司 ３－苯基丙基胺衍生物
CN120152969A (zh) * 2023-10-07 2025-06-13 普美瑞(苏州)生物科技有限公司 一种能降解表皮生长因子受体的化合物及其用途
AU2024374420A1 (en) 2023-11-02 2026-04-16 Kumquat Biosciences Inc. Degraders and uses thereof
WO2025113714A1 (zh) * 2023-12-01 2025-06-05 苏州信诺维医药科技股份有限公司 稠环类化合物、其药物组合物及其应用
WO2025137500A1 (en) 2023-12-21 2025-06-26 Dana-Farber Cancer Institute, Inc. Kinase inhibition and degradation
TW202543650A (zh) 2024-03-08 2025-11-16 美商海爾達醫療運營公司 異雙官能化合物及其在治療疾病中之用途
CN117924286B (zh) * 2024-03-20 2024-05-24 四川大学华西医院 一类喹唑啉-吡咯烷类衍生物及其制备方法
WO2026060321A1 (en) 2024-09-13 2026-03-19 Olema Pharmaceuticals, Inc. Kat6 degrader compounds and method thereof

Family Cites Families (128)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9603095D0 (en) 1996-02-14 1996-04-10 Zeneca Ltd Quinazoline derivatives
DE122007000079I2 (de) 1996-07-24 2010-08-12 Celgene Corp Substituierte 2-(2,6-dioxopiperidin-3-yl)-phthalimide und -1-oxoisoindoline und verfahren zur reduzierung des tnf-alpha-spiegels
CA2287387C (en) 1997-05-14 2010-02-16 Sloan-Kettering Institute For Cancer Research Methods and compositions for destruction of selected proteins
GB9716557D0 (en) 1997-08-06 1997-10-08 Glaxo Group Ltd Benzylidene-1,3-dihydro-indol-2-one derivatives having anti-cancer activity
US6306663B1 (en) 1999-02-12 2001-10-23 Proteinex, Inc. Controlling protein levels in eucaryotic organisms
EP1176959B1 (en) 1999-05-05 2006-03-08 Merck & Co., Inc. Novel prolines as antimicrobial agents
US6921763B2 (en) 1999-09-17 2005-07-26 Abbott Laboratories Pyrazolopyrimidines as therapeutic agents
US7208157B2 (en) 2000-09-08 2007-04-24 California Institute Of Technology Proteolysis targeting chimeric pharmaceutical
WO2002020740A2 (en) 2000-09-08 2002-03-14 California Institute Of Technology Proteolysis targeting chimeric pharmaceutical
US20030045552A1 (en) 2000-12-27 2003-03-06 Robarge Michael J. Isoindole-imide compounds, compositions, and uses thereof
JP2005507363A (ja) 2001-02-16 2005-03-17 イー・アイ・デュポン・ドウ・ヌムール・アンド・カンパニー 血管新生阻害トリペプチド、組成物およびそれらの使用方法
MXPA03008560A (es) 2001-03-22 2004-06-30 Abbot Gmbh & Co Kg Pirazolopirimidinas como agentes terapeuticos.
HN2002000136A (es) 2001-06-11 2003-07-31 Basf Ag Inhibidores de la proteasa del virus hiv, compuestos que contienen a los mismos, sus usos farmaceuticos y los materiales para su sintesis
GB0119249D0 (en) 2001-08-07 2001-10-03 Novartis Ag Organic compounds
US7030141B2 (en) 2001-11-29 2006-04-18 Christopher Franklin Bigge Inhibitors of factor Xa and other serine proteases involved in the coagulation cascade
WO2004005248A1 (en) 2002-07-02 2004-01-15 Novartis Ag Peptide inhibitors of smac protein binding to inhibitor of apoptosis proteins (iap)
US7714139B2 (en) 2003-03-27 2010-05-11 Lankenau Institute For Medcial Research IDO inhibitors and methods of use
EP1651595A2 (en) 2003-05-30 2006-05-03 Rigel Pharmaceuticals, Inc. Ubiquitin ligase inhibitors
US20070281907A1 (en) 2003-12-22 2007-12-06 Watkins William J Kinase Inhibitor Phosphonate Conjugates
BRPI0506883A (pt) 2004-01-16 2007-05-29 Univ Michigan miméticos de smac conformacionalmente comprimidos e seus usos
AU2005228950B2 (en) 2004-03-23 2012-02-02 Genentech, Inc. Azabicyclo-octane inhibitors of IAP
DK2253614T3 (da) 2004-04-07 2013-01-07 Novartis Ag IAP-inhibitorer
KR100984459B1 (ko) 2004-07-02 2010-09-29 제넨테크, 인크. Ｉａｐ의 억제제
DK1836201T4 (da) 2004-12-20 2013-11-11 Genentech Inc Pyrrolidininhibitorer af IAP.
MX2007010371A (es) 2005-02-25 2008-01-11 Tetralogic Pharmaceuticals Inhibidores dimericos iap.
CN100383139C (zh) 2005-04-07 2008-04-23 天津和美生物技术有限公司 可抑制细胞释放肿瘤坏死因子的哌啶-2，6-二酮衍生物
WO2006113942A2 (en) 2005-04-20 2006-10-26 Schering Corporation Method of inhibiting cathepsin activity
UA91560C2 (ru) 2005-08-31 2010-08-10 Селджин Корпорэйшн Соединения ряда изоиндолимидов, их композиция и применение
AU2007226715A1 (en) 2006-03-03 2007-09-20 Novartis Ag N-formyl hydroxylamine compounds
WO2007101347A1 (en) 2006-03-07 2007-09-13 Aegera Therapeutics Inc. Bir domain binding compounds
NZ572531A (en) 2006-05-05 2011-09-30 Univ Michigan Bivalent smac mimetics and the uses thereof
AU2007275415A1 (en) 2006-07-20 2008-01-24 Ligand Pharmaceuticals Incorporated Proline urea CCR1 antagonists for the treatment of autoimmune diseases or inflammation
US20100056495A1 (en) 2006-07-24 2010-03-04 Tetralogic Pharmaceuticals Corporation Dimeric iap inhibitors
RU2448101C2 (ru) 2006-08-30 2012-04-20 Селджин Корпорейшн 5-замещенные изоиндолиновые соединения
CL2007002513A1 (es) 2006-08-30 2008-04-04 Celgene Corp Soc Organizada Ba Compuestos derivados de isoindolina sustituidos, compuestos intermediarios; composicion farmaceutica; y uso en el tratamiento y prevencion de enfermedades tales como cancer, dolor, degeneracion macular, entre otras.
CA2668286C (en) 2006-11-03 2014-09-16 Pharmacyclics, Inc. Bruton's tyrosine kinase activity probe and method of using
WO2008109057A1 (en) 2007-03-02 2008-09-12 Dana-Farber Cancer Institute, Inc. Organic compounds and their uses
JP5454943B2 (ja) 2007-04-12 2014-03-26 ジョイアント ファーマスーティカルズ、インク． 抗癌剤として有用なｓｍａｃ模倣二量体及び三量体
WO2008128171A2 (en) 2007-04-13 2008-10-23 The Regents Of The University Of Michigan Diazo bicyclic smac mimetics and the uses thereof
WO2008134679A1 (en) 2007-04-30 2008-11-06 Genentech, Inc. Inhibitors of iap
US20100203012A1 (en) 2007-05-30 2010-08-12 Aegera Therapeutics, Inc. Iap bir domain binding compounds
US8415340B2 (en) 2007-07-25 2013-04-09 Bristol-Myers Squibb Company Triazine kinase inhibitors
EP2058312A1 (en) 2007-11-09 2009-05-13 Universita' degli Studi di Milano SMAC mimetic compounds as apoptosis inducers
PT2358697E (pt) 2008-10-29 2016-02-03 Celgene Corp Compostos de isoindolina para utilização no tratamento do cancro
WO2010107485A1 (en) 2009-03-17 2010-09-23 The Trustees Of Columbia University In The City Of New York E3 ligase inhibitors
WO2010141805A1 (en) 2009-06-05 2010-12-09 Janssen Pharmaceutica Nv Heterocyclic amides as modulators of trpa1
AU2010273220B2 (en) 2009-07-13 2015-10-15 President And Fellows Of Harvard College Bifunctional stapled polypeptides and uses thereof
US8551955B2 (en) 2009-10-28 2013-10-08 Joyant Pharmaceuticals, Inc. Dimeric Smac mimetics
PL3202460T3 (pl) 2010-02-11 2019-12-31 Celgene Corporation Pochodne arylometoksyizoindoliny i zawierające je kompozycje oraz sposoby ich zastosowania
CN103153335A (zh) 2010-06-30 2013-06-12 布兰代斯大学 小分子靶定的蛋白质降解
WO2012040527A2 (en) 2010-09-24 2012-03-29 The Regents Of The University Of Michigan Deubiquitinase inhibitors and methods for use of the same
EP2635284B1 (en) 2010-11-01 2019-12-18 Celgene CAR LLC Heterocyclic compounds and uses thereof
CA2823837A1 (en) 2010-12-07 2012-06-14 Yale University Small-molecule hydrophobic tagging of fusion proteins and induced degradation of same
WO2012090104A1 (en) 2010-12-31 2012-07-05 Kareus Therapeutics, Sa Methods and compositions for designing novel conjugate therapeutics
AU2012249491B2 (en) 2011-04-29 2016-12-15 Celgene Corporation Methods for the treatment of cancer and inflammatory diseases using cereblon as a predictor
US9376425B2 (en) 2011-09-27 2016-06-28 Amgen, Inc. Heterocyclic compounds as MDM2 inhibitors for the treatment of cancer
EP2776409B1 (en) 2011-11-09 2016-02-03 Ensemble Therapeutics Corporation Macrocyclic compounds for inhibition of inhibitors of apoptosis
WO2013071039A1 (en) 2011-11-09 2013-05-16 Ensemble Therapeutics Macrocyclic compounds for inhibition of inhibitors of apoptosis
KR102668696B1 (ko) * 2012-01-12 2024-05-29 예일 유니버시티 E3 유비퀴틴 리가아제에 의한 표적 단백질 및 다른 폴리펩티드의 증진된 분해를 위한 화합물 및 방법
WO2013106646A2 (en) 2012-01-12 2013-07-18 Yale University Compounds and methods for the inhibition of vcb e3 ubiquitin ligase
CN103374000B (zh) * 2012-04-13 2015-11-11 中国科学院广州生物医药与健康研究院 嘧啶并二氮杂卓类化合物及其药用组合物和应用
WO2013170147A1 (en) 2012-05-11 2013-11-14 Yale University Compounds useful for promoting protein degradation and methods using same
EP2855483B1 (en) 2012-05-24 2017-10-25 Novartis AG Pyrrolopyrrolidinone compounds
BR112014029530A2 (pt) 2012-05-30 2017-06-27 Hoffmann La Roche compostos, composição farmacêutica e uso de um composto
US20150152083A1 (en) * 2012-06-06 2015-06-04 Irm Llc, A Delaware Limited Liability Company Compounds and Compositions for Modulating EGFR Activity
US9345740B2 (en) 2012-07-10 2016-05-24 Bristol-Myers Squibb Company IAP antagonists
ES2742285T3 (es) 2012-07-31 2020-02-13 Novartis Ag Marcadores asociados con la sensibilidad a inhibidores del doble minuto humano 2 (MDM2)
US9453048B2 (en) 2012-08-09 2016-09-27 Bristol-Myers Squibb Company IAP antagonists
TWI586668B (zh) 2012-09-06 2017-06-11 第一三共股份有限公司 二螺吡咯啶衍生物之結晶
US9783573B2 (en) 2012-09-18 2017-10-10 Bristol-Myers Squibb Company IAP antagonists
KR101738063B1 (ko) 2012-09-21 2017-05-19 아로그 파마슈티칼스, 인코퍼레이티드 구조적으로 활성인 인산화된 ｆｌｔ３ 키나제의 억제 방법
US9603889B2 (en) 2012-10-02 2017-03-28 Bristol-Myers Squibb Company IAP antagonists
CA2930030A1 (en) 2012-11-09 2014-05-15 Ensemble Therapeutics Corporation Macrocyclic compounds for inhibition of inhibitors of apoptosis
WO2014081718A1 (en) 2012-11-20 2014-05-30 Genentech, Inc. Aminopyrimidine compounds as inhibitors of t790m containing egfr mutants
KR102196882B1 (ko) 2012-12-20 2020-12-30 머크 샤프 앤드 돔 코포레이션 Hdm2 억제제로서의 치환된 이미다조피리딘
WO2014100071A2 (en) 2012-12-20 2014-06-26 Merck Sharp & Dohme Corp. Substituted pyrrolopyrimidines as hdm2 inhibitors
EP2752191A1 (en) 2013-01-07 2014-07-09 Sanofi Compositions and methods using hdm2 antagonist and mek inhibitor
GB201311910D0 (en) 2013-07-03 2013-08-14 Glaxosmithkline Ip Dev Ltd Novel Compounds
NL2011274C2 (en) 2013-08-06 2015-02-09 Illumicare Ip B V 51 Groundbreaking platform technology for specific binding to necrotic cells.
WO2014134201A1 (en) 2013-02-28 2014-09-04 Amgen Inc. A benzoic acid derivative mdm2 inhibitor for the treatment of cancer
MX374513B (es) 2013-03-14 2025-03-06 Amgen Inc Compuestos de morfolinona de ácido heteroarilo como inhibidores mdm2 para el tratamiento de cáncer.
WO2014210354A1 (en) 2013-06-28 2014-12-31 Genentech, Inc. Azaindazole compounds as inhibitors of t790m containing egfr mutants
GB201311891D0 (en) 2013-07-03 2013-08-14 Glaxosmithkline Ip Dev Ltd Novel compound
GB201311888D0 (en) 2013-07-03 2013-08-14 Glaxosmithkline Ip Dev Ltd Novel compounds
US9637518B2 (en) 2013-07-12 2017-05-02 Bristol-Myers Squibb Company IAP antagonists
CN104418860B (zh) * 2013-08-20 2016-09-07 中国科学院广州生物医药与健康研究院 嘧啶并杂环类化合物及其药用组合物和应用
UA115388C2 (uk) 2013-11-21 2017-10-25 Пфайзер Інк. 2,6-заміщені пуринові похідні та їх застосування в лікуванні проліферативних захворювань
US20150259288A1 (en) 2014-03-14 2015-09-17 City Of Hope 5-bromo-indirubins
US20160058872A1 (en) 2014-04-14 2016-03-03 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use
US20180228907A1 (en) 2014-04-14 2018-08-16 Arvinas, Inc. Cereblon ligands and bifunctional compounds comprising the same
RU2738833C9 (ru) * 2014-04-14 2022-02-28 Арвинас, Оперэйшнз, Инк. Имидные модуляторы протеолиза и способы их применения
JP6468611B2 (ja) 2014-05-13 2019-02-13 アリアド ファーマシューティカルズ， インコーポレイテッド キナーゼ阻害のためのヘテロアリール化合物
TW201613916A (en) 2014-06-03 2016-04-16 Gilead Sciences Inc TANK-binding kinase inhibitor compounds
US20160022642A1 (en) 2014-07-25 2016-01-28 Yale University Compounds Useful for Promoting Protein Degradation and Methods Using Same
US10071164B2 (en) 2014-08-11 2018-09-11 Yale University Estrogen-related receptor alpha based protac compounds and associated methods of use
US9694084B2 (en) 2014-12-23 2017-07-04 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
WO2016105518A1 (en) * 2014-12-23 2016-06-30 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
US12312316B2 (en) 2015-01-20 2025-05-27 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
JP6817962B2 (ja) 2015-01-20 2021-01-20 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． ターゲティングされたアンドロゲン受容体分解のための化合物および方法
GB201504314D0 (en) 2015-03-13 2015-04-29 Univ Dundee Small molecules
EP3270917A4 (en) 2015-03-18 2018-08-08 Arvinas, 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
GB201506872D0 (en) 2015-04-22 2015-06-03 Ge Oil & Gas Uk Ltd Novel compounds
CA2988414C (en) * 2015-06-04 2023-09-26 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use
WO2016197114A1 (en) 2015-06-05 2016-12-08 Arvinas, Inc. Tank-binding kinase-1 protacs and associated methods of use
JP6845165B2 (ja) 2015-06-30 2021-03-17 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 Ｅｇｆｒ阻害剤およびその使用方法
EP3319944A4 (en) 2015-07-10 2019-04-24 Arvinas, Inc. MDM2-BASED MODULATORS OF PROTEOLYSIS AND RELATED USE METHODS
BR112017028269A2 (pt) 2015-07-13 2018-09-04 Arvinas Inc composto, composição farmacêutica, uso de uma quantidade efetiva de um composto, estado ou condição de doença, e, método para identificar um composto.
WO2017024318A1 (en) 2015-08-06 2017-02-09 Dana-Farber Cancer Institute, Inc. Targeted protein degradation to attenuate adoptive t-cell therapy associated adverse inflammatory responses
US10772962B2 (en) 2015-08-19 2020-09-15 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of bromodomain-containing proteins
GB201516243D0 (en) 2015-09-14 2015-10-28 Glaxosmithkline Ip Dev Ltd Novel compounds
BR112018008918A8 (pt) 2015-11-02 2019-02-26 Univ Yale compostos de quimera proteólise dirigida e métodos para preparação e uso dos mesmos
WO2017117474A1 (en) 2015-12-30 2017-07-06 Dana-Farber Cancer Institute, Inc. Bifunctional compounds for her3 degradation and methods of use
US20170281784A1 (en) 2016-04-05 2017-10-05 Arvinas, Inc. Protein-protein interaction inducing technology
AU2017254713C1 (en) 2016-04-22 2021-04-29 Dana-Farber Cancer Institute, Inc. Bifunctional molecules for degradation of EGFR and methods of use
CN109790143A (zh) 2016-05-10 2019-05-21 C4医药公司 用于靶蛋白降解的胺连接的c3-戊二酰亚胺降解决定子体
US10646488B2 (en) 2016-07-13 2020-05-12 Araxes Pharma Llc Conjugates of cereblon binding compounds and G12C mutant KRAS, HRAS or NRAS protein modulating compounds and methods of use thereof
US20180072711A1 (en) 2016-09-15 2018-03-15 Arvinas, Inc. Indole derivatives as estrogen receptor degraders
CN110506039A (zh) 2016-10-11 2019-11-26 阿尔维纳斯股份有限公司 用于雄激素受体靶向降解的化合物和方法
MX2019005007A (es) 2016-11-01 2019-07-18 Arvinas Inc Protac dirigidos a la proteína tau y métodos asociados de uso.
BR112019011200B1 (pt) 2016-12-01 2021-12-28 Arvinas Operations, Inc Derivados de tetrahidronaftaleno e tetrahidroisoquinolina como degradadores do receptor de estrogênio
JP2020505327A (ja) 2016-12-23 2020-02-20 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． Ｅｇｆｒタンパク質分解標的化キメラ分子およびその関連する使用方法
US10806737B2 (en) 2016-12-23 2020-10-20 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of fetal liver kinase polypeptides
KR20250117470A (ko) 2016-12-23 2025-08-04 아비나스 오퍼레이션스, 인코포레이티드 급속 진행성 섬유육종 폴리펩티드의 표적화 분해를 위한 화합물 및 방법
US11191741B2 (en) 2016-12-24 2021-12-07 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of enhancer of zeste homolog 2 polypeptide
BR112019015312A2 (pt) 2017-01-26 2020-03-10 Arvinas Operations, Inc. Moduladores da proteólise pelo receptor de estrogênio e métodos de uso associados
IL312367A (en) 2017-01-31 2024-06-01 Arvinas Operations Inc Cereblon ligands and bifunctional compounds comprising the same
JP7227912B2 (ja) 2017-02-08 2023-02-24 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 キメラ抗原受容体の調節

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