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Structure-based development of potent and selective type-II kinase inhibitors of RIPK1

文献类型：期刊论文

作者Qin, Ying2,3; Li, Dekang2,3; Qi, Chunting2; Xiang, Huaijiang2,3; Meng, Huyan2,3; Liu, Jingli2; Zhou, Shaoqing2,3; Gong, Xinyu3,4; Li, Ying2,3,4; Xu, Guifang2
刊名ACTA PHARMACEUTICA SINICA B
出版日期2024
卷号14期号:1页码:319-334
ISSN号2211-3835
关键词RIPK1 Necroptosis Type-II kinase inhibitors Rational design Lead optimization Structure-activity relationship Anti-inflammation Preclinical drug discovery
DOI10.1016/j.apsb.2023.10.021
通讯作者Li, Ying(liying@sioc.ac.cn) ; Tan, Li(tanli@sioc.ac.cn)
英文摘要Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure -guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development. 2024 The Authors. Published by Elsevier B.V. on behalf of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. This is an open access article under the CC BY -NCND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
WOS关键词INTERACTING PROTEIN-1 RIP1 ; CELL-DEATH ; DISCOVERY ; DESIGN ; IDENTIFICATION ; NECROPTOSIS
资助项目National Natural Science Foundation of China[21837004] ; National Natural Science Foundation of China[82151212] ; National Natural Science Foundation of China[32170755] ; Strategic Priority Research Program of the Chinese Academy of Sciences (China)[XDB39050500] ; Shanghai Municipal Science and Technology Major Project (China)[2019SHZDZX02]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
WOS记录号WOS:001154148000001
源URL[http://119.78.100.183/handle/2S10ELR8/309057]  
专题中国科学院上海药物研究所
通讯作者Li, Ying; Tan, Li
作者单位1.Shenzhen Univ, Shenzhen Peoples Hosp 2, Shenzhen Inst Translat Med, Dept Burn & Plast Surg,Affiliated Hosp 1,Med Sch, Shenzhen 518035, Peoples R China
2.Chinese Acad Sci, Interdisciplinary Res Ctr Biol & Chem, Shanghai Inst Organ Chem, Shanghai 201210, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Chem Biol, Shanghai 200032, Peoples R China
5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
6.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
7.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Affiliated Hosp 2, Inst Hepatol,Sch Med ,Natl Clin Res Ctr Infect Dis, Shenzhen 518112, Peoples R China
推荐引用方式
GB/T 7714		 Qin, Ying,Li, Dekang,Qi, Chunting,et al. Structure-based development of potent and selective type-II kinase inhibitors of RIPK1[J]. ACTA PHARMACEUTICA SINICA B,2024,14(1):319-334.
APA Qin, Ying.,Li, Dekang.,Qi, Chunting.,Xiang, Huaijiang.,Meng, Huyan.,...&Tan, Li.(2024).Structure-based development of potent and selective type-II kinase inhibitors of RIPK1.ACTA PHARMACEUTICA SINICA B,14(1),319-334.
MLA Qin, Ying,et al."Structure-based development of potent and selective type-II kinase inhibitors of RIPK1".ACTA PHARMACEUTICA SINICA B 14.1(2024):319-334.

入库方式： OAI收割

来源：上海药物研究所

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