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Discovery of thalidomide-based PROTAC small molecules as the highly efficient SHP2 degraders

文献类型：期刊论文

作者Yang, Xiangbo1,4; Wang, Zhijia2,3; Pei, Yuan1,4; Song, Ning2,4,5; Xu, Lei2; Feng, Bo2,6; Wang, Hanlin2,7; Luo, Xiaomin2,8; Hu, Xiaobei2; Qiu, Xiaohui2
刊名EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版日期2021-06-05
卷号218页码:14
ISSN号0223-5234
关键词SHP2 degradation Proteolysis targeting chimera (PROTAC) Thalidomide-based heterobifunctional molecules E3 ubiquitin ligase CRBN
DOI10.1016/j.ejmech.2021.113341
通讯作者Zhou, Yubo(ybzhou@simm.ac.cn) ; Li, Jia(jli@simm.ac.cn) ; Zhou, Bing(zhoubing@simm.ac.cn)
英文摘要SHP2, a non-receptor tyrosine phosphatase, plays a pivotal role in numerous oncogenic cell-signaling cascades like RAS-ERK, PI3K-AKT and JAK-STAT. On the other hand, proteolysis targeting chimera (PROTAC) has emerged as a promising strategy for the degradation of disease-related protein of interest (POI). SHP2 degradation via the PROTAC strategy will provide an alternative startegy for SHP2-mediated cancer therapy. Herein we described the design, synthesis and evaluation of a series of thalidomide-based heterobifunctional molecules and identified 11(ZB-S-29) as the highly efficient SHP2 degrader with a DC50 of 6.02 nM. Further mechanism investigation illustrated that 11 came into function through targeted SHP2 protein degradation. (c) 2021 Elsevier Masson SAS. All rights reserved.
WOS关键词E3 UBIQUITIN LIGASE ; POTENT ; PTPN11 ; DEGRADATION ; PHOSPHATASE ; MUTATIONS ; BROMODOMAIN ; PROTEINS ; COMPLEX
资助项目National Natural Science Foundation of China[81973166] ; National Natural Science Foundation of China[21702218] ; National Natural Science Foundation of China[21772068] ; National Natural Science Foundation of China[81773779] ; National Natural Science Foundation of China[81773568] ; National Natural Science Foundation of China[91753207] ; National Science and Technology Major Project of China[2018ZX09711002-008-004] ; National Science and Technology Major Project of China[2018ZX09711002-008-005] ; National Science and Technology Major Project of China[2018ZX09711002-006-001] ; K. C. Wong Education Foundation ; Youth innovation promotion association[2017333]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号WOS:000646195900003
源URL[http://119.78.100.183/handle/2S10ELR8/297366]  
专题新药研究国家重点实验室
通讯作者Zhou, Yubo; Li, Jia; Zhou, Bing
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Jiangnan Univ, Sch Pharmaceut Sci, Wuxi 214122, Jiangsu, Peoples R China
4.Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China
5.ShanghaiTech Univ, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China
6.Shenyang Pharmaceut Univ, Sch Life Sci & Biopharmaceut, 103 Wenhua Rd, Shenyang, Liaoning, Peoples R China
7.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
8.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210046, Peoples R China
9.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou 310024, Peoples R China
推荐引用方式
GB/T 7714		 Yang, Xiangbo,Wang, Zhijia,Pei, Yuan,et al. Discovery of thalidomide-based PROTAC small molecules as the highly efficient SHP2 degraders[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2021,218:14.
APA Yang, Xiangbo.,Wang, Zhijia.,Pei, Yuan.,Song, Ning.,Xu, Lei.,...&Zhou, Bing.(2021).Discovery of thalidomide-based PROTAC small molecules as the highly efficient SHP2 degraders.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,218,14.
MLA Yang, Xiangbo,et al."Discovery of thalidomide-based PROTAC small molecules as the highly efficient SHP2 degraders".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 218(2021):14.

入库方式： OAI收割

来源：上海药物研究所

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