KR20190101406A - Egfr 단백질분해 표적화 키메라 분자 및 관련 사용 방법 - Google Patents

Egfr 단백질분해 표적화 키메라 분자 및 관련 사용 방법 Download PDF

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KR20190101406A
KR20190101406A KR1020197021538A KR20197021538A KR20190101406A KR 20190101406 A KR20190101406 A KR 20190101406A KR 1020197021538 A KR1020197021538 A KR 1020197021538A KR 20197021538 A KR20197021538 A KR 20197021538A KR 20190101406 A KR20190101406 A KR 20190101406A
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alkyl
optionally substituted
substituted
aryl
heteroaryl
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Korean (ko)
Inventor
앤드류 피. 크루
커트 짐머만
징 왕
미카엘 벨린
한칭 동
알렉세이 이셴코
이민 치안
크레이그 엠. 크루즈
사울 제이미-피게로아
조지 버슬렘
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아비나스 오퍼레이션스, 인코포레이티드
예일 유니버시티
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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
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    • 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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    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
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  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Dermatology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Neurology (AREA)
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  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Cardiology (AREA)
  • Neurosurgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
KR1020197021538A 2016-12-23 2017-12-22 Egfr 단백질분해 표적화 키메라 분자 및 관련 사용 방법 Ceased KR20190101406A (ko)

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

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KR20190101406A true KR20190101406A (ko) 2019-08-30

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KR1020197021538A Ceased KR20190101406A (ko) 2016-12-23 2017-12-22 Egfr 단백질분해 표적화 키메라 분자 및 관련 사용 방법

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=)

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* 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
WO2017011371A1 (en) 2015-07-10 2017-01-19 Arvinas, Inc Mdm2-based modulators of proteolysis and associated methods of use
EP3337476A4 (en) 2015-08-19 2019-09-04 Arvinas, 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
EP3445357B1 (en) * 2016-04-22 2021-05-26 Dana-Farber Cancer Institute, Inc. Bifunctional molecules for degradation of egfr and methods of use
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
EP4491236A3 (en) 2016-05-10 2025-04-02 C4 Therapeutics, Inc. Heterocyclic degronimers for target protein degradation
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
EP3454862B1 (en) 2016-05-10 2024-09-11 C4 Therapeutics, Inc. Spirocyclic degronimers for target protein degradation
WO2018053354A1 (en) 2016-09-15 2018-03-22 Arvinas, Inc. Indole derivatives as estrogen receptor degraders
EP3532464A4 (en) 2016-10-28 2020-07-08 Icahn School of Medicine at Mount Sinai COMPOSITIONS AND METHODS FOR THE TREATMENT OF EZH2 MEDIATION CANCER
IL290809B2 (en) * 2016-11-01 2024-01-01 Arvinas Operations Inc Tau-protein targeting protacs and associated methods of use
KR102674902B1 (ko) 2016-12-01 2024-06-14 아비나스 오퍼레이션스, 인코포레이티드 에스트로겐 수용체 분해제로서의 테트라히드로나프탈렌 및 테트라히드로이소퀴놀린 유도체
US10806737B2 (en) 2016-12-23 2020-10-20 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of fetal liver kinase polypeptides
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US11173211B2 (en) 2016-12-23 2021-11-16 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides
MX2019007646A (es) 2016-12-23 2019-09-06 Arvinas Operations Inc Moleculas quimericas dirigidas a la proteolisis del egfr y metodos asociados de uso.
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
AU2018211975B2 (en) 2017-01-26 2022-05-26 Arvinas Operations, Inc. Modulators of estrogen receptor proteolysis and associated methods of use
BR112019015484A2 (pt) 2017-01-31 2020-04-28 Arvinas Operations Inc ligantes de cereblon e compostos bifuncionais compreendendo os mesmos
WO2018226542A1 (en) * 2017-06-09 2018-12-13 Arvinas, Inc. Modulators of proteolysis and associated methods of use
EP4717317A2 (en) 2017-06-20 2026-04-01 C4 Therapeutics, Inc. N/o-linked degrons and degronimers for protein degradation
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
CN118206529A (zh) 2017-09-04 2024-06-18 C4医药公司 二氢苯并咪唑酮
CN111278816B (zh) 2017-09-04 2024-03-15 C4医药公司 二氢喹啉酮
CN118108706A (zh) 2017-09-04 2024-05-31 C4医药公司 戊二酰亚胺
WO2019094772A1 (en) 2017-11-10 2019-05-16 The Regents Of The University Of Michigan Ash1l degraders and methods of treatment therewith
EP3710002A4 (en) 2017-11-16 2021-07-07 C4 Therapeutics, Inc. DEGRADER AND DEGRONE FOR TARGETED PROTEIN DEGRADATION
US11065231B2 (en) 2017-11-17 2021-07-20 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
US11220515B2 (en) 2018-01-26 2022-01-11 Yale University Imide-based modulators of proteolysis and associated 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)
JP2021519337A (ja) 2018-03-26 2021-08-10 シー４ セラピューティクス， インコーポレイテッド Ｉｋａｒｏｓの分解のためのセレブロン結合剤
US12539292B2 (en) 2018-04-01 2026-02-03 Arvinas Operations, Inc. BRM targeting compounds and associated methods of use
KR20210006356A (ko) * 2018-04-04 2021-01-18 아비나스 오퍼레이션스, 인코포레이티드 단백질분해 조절제 및 연관된 사용 방법
CN110357889B (zh) * 2018-04-09 2022-03-15 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
CN119751456A (zh) 2018-04-16 2025-04-04 C4医药公司 螺环化合物
EP3578561A1 (en) 2018-06-04 2019-12-11 F. Hoffmann-La Roche AG Spiro compounds
CA3104298A1 (en) 2018-06-21 2019-12-26 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
DK3820573T3 (da) 2018-07-10 2023-10-23 Novartis Ag 3-(5-hydroxy-1-oxoisoindolin-2-yl)piperidin-2,6-dion-derivativer og anvendelse deraf ved behandling af ikaros family zinc finger 2 (ikzf2)-afhængige sygdomme
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
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
US11969472B2 (en) 2018-08-22 2024-04-30 Cullgen (Shanghai), Inc. Tropomyosin receptor kinase (TRK) degradation compounds and methods of use
MX2021001957A (es) 2018-08-22 2021-07-15 Cullgen Shanghai Inc Compuestos de degradacion y metodos de uso del receptor de tropomiosina quinasa (trk).
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)
JP7623943B2 (ja) 2018-11-30 2025-01-29 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
CN120698983A (zh) 2018-12-20 2025-09-26 C4医药公司 靶向蛋白降解
AU2020205665C1 (en) * 2019-01-09 2025-10-02 Dana-Farber Cancer Institute, Inc. DOT1L degraders and uses thereof
WO2020162725A1 (ko) * 2019-02-07 2020-08-13 한국화학연구원 표적 단백질 ｅｅｄ 분해 유도 데그라듀서, 이의 제조방법 및 이를 유효성분으로 함유하는 ｅｅｄ, ｅｚｈ2, 또는 ｐｒｃ2 관련 질환의 예방 또는 치료용 약학적 조성물
EP3932922A4 (en) 2019-02-25 2022-05-11 ShanghaiTech University SULPHUR-CONTAINING COMPOUND BASED ON A GLUTARIMIDE FRAMEWORK AND ITS USE
WO2020181232A1 (en) 2019-03-06 2020-09-10 C4 Therapeutics, Inc. Heterocyclic compounds for medical treatment
AU2020247255A1 (en) * 2019-03-28 2021-11-11 Essa Pharma, Inc. Androgen receptor modulators and methods for use as Proteolysis Targeting Chimera ligands
CN120172958A (zh) 2019-04-12 2025-06-20 C4医药公司 Ikaros和aiolos的三环降解物
US12414995B2 (en) 2019-04-16 2025-09-16 Northwestern University Bifunctional compounds comprising Apcin-A and their use in the treatment of cancer
CN118908962A (zh) 2019-05-06 2024-11-08 西奈山伊坎医学院 作为hpk1的降解剂的异双功能化合物
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
BR112021026517A2 (pt) 2019-06-28 2022-05-10 Kymera Therapeutics Inc Degradadores de irak e usos dos mesmos
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
WO2021011868A1 (en) 2019-07-17 2021-01-21 Kymera Therapeutics, Inc. Irak degraders and uses thereof
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
JP7593998B2 (ja) * 2019-08-23 2024-12-03 北京泰徳製薬股▲フン▼有限公司 Ｅｇｆｒおよびａｌｋを阻害してそれらの分解を阻害する化合物
IL320609A (en) 2019-08-26 2025-07-01 Arvinas Operations Inc Methods for treating breast cancer with a history of tetrahydronaphthalene as estrogen receptor-disrupting agents
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
IL326879A (en) 2019-11-11 2026-04-01 Dana Farber Cancer Inst Inc EGFR allosteric inhibitors and methods of using them
CA3161455A1 (en) * 2019-11-13 2021-05-20 Aprinoia Therapeutics Limited Compounds for degrading tau protein aggregates and uses thereof
AU2020387392B2 (en) 2019-11-19 2025-09-11 Bristol-Myers Squibb Company Compounds useful as inhibitors of Helios protein
US12551564B2 (en) 2019-12-10 2026-02-17 Kymera Therapeutics, Inc. IRAK degraders and uses thereof
KR20220114615A (ko) * 2019-12-16 2022-08-17 베이징 타이드 파마슈티컬 코퍼레이션 리미티드 Egfr 키나제의 분해를 억제 및 유도하는 화합물
WO2021127190A1 (en) 2019-12-17 2021-06-24 Kymera Therapeutics, Inc. Irak degraders and uses thereof
JP7682181B2 (ja) 2019-12-18 2025-05-23 ノバルティス アーゲー ３－（５－メトキシ－１－オキソイソインドリン－２－イル）ピペリジン－２，６－ジオン誘導体及びその使用
CA3165168A1 (en) 2019-12-19 2021-06-24 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
BR112022011827A2 (pt) 2019-12-20 2022-08-30 C4 Therapeutics Inc Composto, composição farmacêutica, uso de um composto, métodos para tratamento ou profilaxia de câncer e para tratar um paciente com um distúrbio mediado por receptor do fator de crescimento epidérmico, e, invenção
WO2023205701A1 (en) 2022-04-20 2023-10-26 Kumquat Biosciences Inc. Macrocyclic heterocycles and uses thereof
CA3173262A1 (en) 2020-02-26 2021-09-02 Cullgen (Shanghai), Inc. Tropomyosin receptor kinase (trk) degradation compounds and methods of use
AU2021231898A1 (en) 2020-03-05 2022-10-27 C4 Therapeutics, Inc. Compounds for targeted degradation of BRD9
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)
EP4157833A1 (en) * 2020-05-28 2023-04-05 Bristol-Myers Squibb Company Galectin-3 inhibitors
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
WO2021255212A1 (en) 2020-06-19 2021-12-23 F. Hoffmann-La Roche Ag Braf degraders
CN113912589B (zh) * 2020-07-08 2023-10-20 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
EP4192458A4 (en) 2020-08-05 2024-09-04 C4 Therapeutics, Inc. COMPOUNDS FOR TARGETED DEGRADATION 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
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
US20230322723A1 (en) * 2020-09-11 2023-10-12 J2H Biotech Inc. Compounds for suppressing egfr mutant cancer and pharmaceutical use thereof
JP7685044B2 (ja) * 2020-09-13 2025-05-28 山東博安生物技術股▲ふん▼有限公司 受容体ｔａｃ技術による膜結合タンパク質の下方制御
AR123492A1 (es) 2020-09-14 2022-12-07 Arvinas Operations Inc Formas cristalinas y amorfas de un compuesto para la degradación dirigida del receptor de estrógeno
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
PH12023500015A1 (en) 2020-12-30 2024-03-11 Kymera Therapeutics Inc Irak degraders and uses thereof
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
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
US20240165243A1 (en) 2021-02-10 2024-05-23 Beigene Switzerland Gmbh Egfr degraders and methods of use
CN116867494A (zh) 2021-02-15 2023-10-10 凯麦拉医疗公司 Irak4降解剂和其用途
WO2022174268A1 (en) 2021-02-15 2022-08-18 Kymera Therapeutics, Inc. Irak4 degraders and uses thereof
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
BR112023020077A2 (pt) 2021-04-06 2023-11-14 Bristol Myers Squibb Co Compostos de oxoisoindolina substituída por piridinila
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
CN115232114B (zh) * 2021-04-23 2023-12-19 上海领泰生物医药科技有限公司 Sos1降解剂及其制备方法和应用
WO2022228556A1 (en) * 2021-04-30 2022-11-03 Beigene, Ltd. Egfr degraders and associated methods of use
KR20240017814A (ko) 2021-05-05 2024-02-08 바이오젠 엠에이 인코포레이티드 브루톤 티로신 키나제의 분해를 표적으로 하는 화합물
WO2022251588A1 (en) * 2021-05-27 2022-12-01 Halda Therapeutics Opco, Inc. Heterobifunctional compounds and methods of treating disease
PY2243958A (es) 2021-06-03 2023-01-20 Novartis Ag Derivados de 3–(5–oxi)–1–oxoisoindolin–2–il)piperidina–2,6–diona y sus usos
US20240293386A1 (en) * 2021-06-22 2024-09-05 Lg Chem, Ltd. Novel compound as protein kinase inhibitor
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
US20250129047A1 (en) 2021-07-04 2025-04-24 Newave Pharmaceutical Inc. Isoquinoline derivatives as mutant egfr modulators and uses thereof
KR20240035526A (ko) 2021-07-07 2024-03-15 바이오젠 엠에이 인코포레이티드 Irak4 단백질의 분해를 표적하는 화합물
WO2023283372A1 (en) 2021-07-07 2023-01-12 Biogen Ma Inc. Compounds for targeting degradation of irak4 proteins
KR20240035820A (ko) 2021-07-09 2024-03-18 플렉시움 인코포레이티드 Ikzf2를 조절하는 아릴 화합물 및 약학 조성물
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
US12187744B2 (en) 2021-10-29 2025-01-07 Kymera Therapeutics, Inc. IRAK4 degraders and synthesis thereof
EP4434978A4 (en) * 2021-11-17 2025-03-26 TYK Medicines Inc. Compound for degrading EGFR protein and use thereof
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
EP4472967A4 (en) 2022-01-31 2026-04-15 Kymera Therapeutics Inc Iraqi Degradation Agents and Their Uses
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
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
JP2025523393A (ja) 2022-06-06 2025-07-23 シーフォー セラピューティクス， インコーポレイテッド 二環式置換グルタルイミドセレブロンバインダー
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
EP4584258A1 (en) 2022-09-07 2025-07-16 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
EP4630422A1 (en) * 2022-12-08 2025-10-15 Risen (Suzhou) Pharma Tech Co., Ltd. Bifunctional compounds and pharmaceutical uses thereof
CN121419983A (zh) 2023-01-26 2026-01-27 阿尔维纳斯运营股份有限公司 基于小脑蛋白的kras降解protac及其相关用途
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
CN120981456A (zh) 2023-05-24 2025-11-18 金橘生物科技公司 杂环化合物及其用途
AU2024281173A1 (en) 2023-05-31 2025-12-04 Beone Medicines I Gmbh Compounds for the degradation of egfr kinase
AU2024307234A1 (en) 2023-06-30 2026-01-29 Kumquat Biosciences Inc. Substituted condensed tricyclic amine compounds and uses thereof as ras inhibitors
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
CN121925410A (zh) 2023-09-29 2026-04-24 第一三共株式会社 3-苯基丙胺衍生物
WO2025073251A1 (zh) * 2023-10-07 2025-04-10 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
WO2025096855A1 (en) 2023-11-02 2025-05-08 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
NZ333903A (en) 1996-07-24 2000-02-28 Celgene Corp Substituted 2(2,6-dioxopiperidin-3-yl)phthalimides and -1oxoisoindolines and method of reducing TNF-alpha levels in a mammal
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
US6333344B1 (en) 1999-05-05 2001-12-25 Merck & Co. Prolines as antimicrobial agents
US6921763B2 (en) 1999-09-17 2005-07-26 Abbott Laboratories Pyrazolopyrimidines as therapeutic agents
US7041298B2 (en) 2000-09-08 2006-05-09 California Institute Of Technology Proteolysis targeting chimeric pharmaceutical
US7208157B2 (en) 2000-09-08 2007-04-24 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
CA2432932A1 (en) 2001-02-16 2002-08-29 Mark A. Scialdone Angiogenesis-inhibitory tripeptides, compositions and their methods of use
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)
WO2004094409A1 (en) 2003-03-27 2004-11-04 Lankenau Institute For Medical Research Novel ido inhibitors and methods of use
US7915293B2 (en) 2003-05-30 2011-03-29 Rigel Pharmaceuticals, Inc. Ubiquitin ligase inhibitors
US20070281907A1 (en) 2003-12-22 2007-12-06 Watkins William J Kinase Inhibitor Phosphonate Conjugates
US7932382B2 (en) 2004-01-16 2011-04-26 The Regents Of The University Of Michigan Conformationally constrained Smac mimetics and the uses thereof
WO2005094818A1 (en) 2004-03-23 2005-10-13 Genentech, Inc. Azabicyclo-octane inhibitors of iap
RS52545B (sr) 2004-04-07 2013-04-30 Novartis Ag Inhibitori protein apoptoze (iap)
BRPI0511350A (pt) 2004-07-02 2007-12-04 Genentech Inc composto, métodos de indução da apoptose em uma célula, de sensibilização de uma célula à um sinal apoptótico, de inibição da ligação de uma proteìna iap e de tratamento de uma doença e cáncer e usos de um composto
MX2007007195A (es) 2004-12-20 2007-10-08 Genentech Inc Inhibidores de pirrolidina de iap.
ES2456671T3 (es) 2005-02-25 2014-04-23 Tetralogic Pharmaceuticals Corporation Inhibidores diméricos de 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
KR20080042158A (ko) 2005-08-31 2008-05-14 셀진 코포레이션 이소인돌-이미드 화합물과 이를 포함하는 조성물 및 이를이용한 방법
BRPI0708524A2 (pt) 2006-03-03 2011-05-31 Novartis Ag compostos de n-formil hidroxilamina
WO2007101347A1 (en) 2006-03-07 2007-09-13 Aegera Therapeutics Inc. Bir domain binding compounds
JP5230610B2 (ja) 2006-05-05 2013-07-10 ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン 二価ｓｍａｃ模倣物およびその使用
JP2009544620A (ja) 2006-07-20 2009-12-17 リガンド・ファーマシューティカルズ・インコーポレイテッド 自己免疫疾患及び炎症のためのプロリン尿素ｃｃｒ１アンタゴニスト
US20100056495A1 (en) 2006-07-24 2010-03-04 Tetralogic Pharmaceuticals Corporation Dimeric iap inhibitors
MX2009001989A (es) 2006-08-30 2009-03-09 Celgene Corp Compuestos de isoindolina 5-substituidos.
RU2448101C2 (ru) 2006-08-30 2012-04-20 Селджин Корпорейшн 5-замещенные изоиндолиновые соединения
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
PE20130150A1 (es) 2007-04-30 2013-02-27 Genentech Inc Inhibidores de las iap
WO2008144925A1 (en) 2007-05-30 2008-12-04 Aegera Therapeutics Inc. Iap bir domain binding compounds
KR20100038108A (ko) 2007-07-25 2010-04-12 브리스톨-마이어스 스큅 컴퍼니 트리아진 키나제 억제제
EP2058312A1 (en) 2007-11-09 2009-05-13 Universita' degli Studi di Milano SMAC mimetic compounds as apoptosis inducers
PE20110547A1 (es) 2008-10-29 2011-08-04 Celgene Corp Compuestos de isoindolina con actividad anticancerigena
US20120135089A1 (en) 2009-03-17 2012-05-31 Stockwell Brent R E3 ligase inhibitors
WO2010141805A1 (en) 2009-06-05 2010-12-09 Janssen Pharmaceutica Nv Heterocyclic amides as modulators of trpa1
JP2012532929A (ja) 2009-07-13 2012-12-20 プレジデント アンド フェロウズ オブ ハーバード カレッジ 二機能性のステープリングされたポリペプチドおよびそれらの使用
EP2784076A1 (en) 2009-10-28 2014-10-01 Joyant Pharmaceuticals, Inc. Dimeric SMAC mimetics
EP2536706B1 (en) 2010-02-11 2017-06-14 Celgene Corporation Arylmethoxy isoindoline derivatives and compositions comprising and methods of using the same
SG186389A1 (en) 2010-06-30 2013-01-30 Univ Brandeis Small-molecule-targeted protein degradation
EP2619184B1 (en) 2010-09-24 2018-05-23 The Regents of the University of Michigan Deubiquitinase inhibitors and methods for use of the same
MX382354B (es) 2010-11-01 2025-03-13 Celgene Car Llc Compuestos heterocíclicos y usos de los mismos.
AU2011338615B2 (en) 2010-12-07 2017-07-27 Yale University Small-molecule hydrophobic tagging of fusion proteins and induced degradation of same
US20140243282A1 (en) 2010-12-31 2014-08-28 Satish Reddy Kallam Methods and compositions for designing novel conjugate therapeutics
CA2834535A1 (en) 2011-04-29 2012-11-01 Celgene Corporation Methods for the treatment of cancer and inflammatory diseases using cereblon as a predictor
MX352672B (es) 2011-09-27 2017-12-04 Amgen Inc Compuestos heterocíclicos como inhibidores de mdm2 para el tratamiento del cáncer.
WO2013071039A1 (en) 2011-11-09 2013-05-16 Ensemble Therapeutics Macrocyclic compounds for inhibition of inhibitors of apoptosis
WO2013071035A1 (en) 2011-11-09 2013-05-16 Ensemble Therapeutics Macrocyclic compounds for inhibition of inhibitors of apoptosis
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
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
US20150119435A1 (en) 2012-05-11 2015-04-30 Yale University Compounds useful for promoting protein degradation and methods using same
EP2855483B1 (en) 2012-05-24 2017-10-25 Novartis AG Pyrrolopyrrolidinone compounds
NZ631477A (en) 2012-05-30 2016-12-23 Hoffmann La Roche Substituted pyrrolidine-2-carboxamides
CN104520291A (zh) * 2012-06-06 2015-04-15 Irm责任有限公司 用于调节egfr活性的化合物和组合物
US9345740B2 (en) 2012-07-10 2016-05-24 Bristol-Myers Squibb Company IAP antagonists
US9371568B2 (en) 2012-07-31 2016-06-21 Novartis Ag Markers associated with human double minute 2 inhibitors
WO2014025759A1 (en) 2012-08-09 2014-02-13 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
WO2014047024A1 (en) 2012-09-18 2014-03-27 Bristol-Myers Squibb Company Iap antagonists
JP6407504B2 (ja) 2012-09-21 2018-10-17 アログ・ファーマシューティカルズ・インコーポレイテッドＡｒｏｇ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． 恒常的に活性であるリン酸化型ｆｌｔ３キナーゼの阻害方法
US9603889B2 (en) 2012-10-02 2017-03-28 Bristol-Myers Squibb Company IAP antagonists
TW201428002A (zh) 2012-11-09 2014-07-16 必治妥美雅史谷比公司 用於抑制細胞凋亡抑制劑之巨環化合物
RU2015118647A (ru) 2012-11-20 2017-01-10 Дженентек, Инк. Аминопиримидиновые соединения в качестве ингибиторов содержащих т790м мутантных egfr
TW201429969A (zh) 2012-12-20 2014-08-01 Merck Sharp & Dohme 作爲ｈｄｍ２抑制劑之經取代咪唑吡啶
US9637493B2 (en) 2012-12-20 2017-05-02 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.
CA2902856C (en) 2013-02-28 2021-02-16 Amgen Inc. A benzoic acid derivative mdm2 inhibitor for the treatment of cancer
AU2014236812B2 (en) 2013-03-14 2018-03-01 Amgen Inc. Heteroaryl acid morpholinone compounds as MDM2 inhibitors for the treatment of cancer
WO2014210354A1 (en) 2013-06-28 2014-12-31 Genentech, Inc. Azaindazole compounds as inhibitors of t790m containing egfr mutants
GB201311888D0 (en) 2013-07-03 2013-08-14 Glaxosmithkline Ip Dev Ltd Novel compounds
GB201311891D0 (en) 2013-07-03 2013-08-14 Glaxosmithkline Ip Dev Ltd Novel compound
EP3019517A1 (en) 2013-07-12 2016-05-18 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
US20180228907A1 (en) 2014-04-14 2018-08-16 Arvinas, Inc. Cereblon ligands and bifunctional compounds comprising the same
US20160058872A1 (en) 2014-04-14 2016-03-03 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use
AU2015247817C1 (en) * 2014-04-14 2022-02-10 Arvinas Operations, Inc. Imide-based modulators of proteolysis and associated methods of use
EP3143015B1 (en) 2014-05-13 2019-02-20 ARIAD Pharmaceuticals, Inc. Heteroaryl compounds for kinase inhibition
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
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
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
US12312316B2 (en) 2015-01-20 2025-05-27 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
GB201504314D0 (en) 2015-03-13 2015-04-29 Univ Dundee Small molecules
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
GB201506872D0 (en) 2015-04-22 2015-06-03 Ge Oil & Gas Uk Ltd Novel compounds
HUE054149T2 (hu) * 2015-06-04 2021-08-30 Arvinas Operations Inc Proteolízis imid-alapú modulátorai és ezekkel kapcsolatos felhasználási eljárások
WO2016197114A1 (en) 2015-06-05 2016-12-08 Arvinas, Inc. Tank-binding kinase-1 protacs and associated methods of use
CA2987914C (en) 2015-06-30 2022-09-13 Dana-Farber Cancer Institute, Inc. Inhibitors of egfr and methods of use thereof
WO2017011371A1 (en) 2015-07-10 2017-01-19 Arvinas, Inc Mdm2-based modulators of proteolysis and associated methods of use
CA2988436A1 (en) 2015-07-13 2017-01-19 Arvinas, Inc. Alanine-based modulators of proteolysis and associated methods of use
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
EP3337476A4 (en) 2015-08-19 2019-09-04 Arvinas, 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
AU2016349781A1 (en) * 2015-11-02 2018-05-10 Yale University Proteolysis targeting chimera compounds and methods of preparing and using same
US20190016703A1 (en) 2015-12-30 2019-01-17 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
EP3445357B1 (en) * 2016-04-22 2021-05-26 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
WO2018053354A1 (en) 2016-09-15 2018-03-22 Arvinas, Inc. Indole derivatives as estrogen receptor degraders
WO2018071606A1 (en) 2016-10-11 2018-04-19 Arvinas, Inc. Compounds and methods for the targeted degradation of androgen receptor
IL290809B2 (en) 2016-11-01 2024-01-01 Arvinas Operations Inc Tau-protein targeting protacs and associated methods of use
KR102674902B1 (ko) 2016-12-01 2024-06-14 아비나스 오퍼레이션스, 인코포레이티드 에스트로겐 수용체 분해제로서의 테트라히드로나프탈렌 및 테트라히드로이소퀴놀린 유도체
CN117510491A (zh) 2016-12-23 2024-02-06 阿尔维纳斯运营股份有限公司 用于迅速加速性纤维肉瘤多肽的靶向降解的化合物和方法
MX2019007646A (es) 2016-12-23 2019-09-06 Arvinas Operations Inc Moleculas quimericas dirigidas a la proteolisis del egfr y metodos asociados de uso.
US10806737B2 (en) 2016-12-23 2020-10-20 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of fetal liver kinase polypeptides
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
AU2018211975B2 (en) 2017-01-26 2022-05-26 Arvinas Operations, Inc. Modulators of estrogen receptor proteolysis and associated methods of use
BR112019015484A2 (pt) 2017-01-31 2020-04-28 Arvinas Operations Inc ligantes de cereblon e compostos bifuncionais compreendendo os mesmos
EP3580212A4 (en) 2017-02-08 2021-03-17 Dana Farber Cancer Institute, Inc. REGULATION OF CHEMERIC ANTIGEN RECEPTORS

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

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