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

doi:10.1016/j.ejmech.2021.113341

	Discovery of thalidomide-based PROTAC small molecules as the highly efficient SHP2 degraders
	Yang, Xiangbo 1,4; Wang, Zhijia 2,3; Pei, Yuan 1,4; Song, Ning2,4,5 ; Xu, Lei 2; Feng, Bo 2,6; Wang, Hanlin 2,7; Luo, Xiaomin 2,8; Hu, Xiaobei 2; Qiu, Xiaohui 2; Feng, Huijin 1; Yang, Yaxi 1,4; Zhou, Yubo 2,4; Li, Jia2,4,5,6,8 ; Zhou, Bing 1,4,9
	2021
发表期刊	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (IF:6.0[JCR-2023],6.1[5-Year])
ISSN	0223-5234
EISSN	1768-3254
卷号	218
DOI	10.1016/j.ejmech.2021.113341
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.
关键词	SHP2 degradation Proteolysis targeting chimera (PROTAC) Thalidomide-based heterobifunctional molecules E3 ubiquitin ligase CRBN
收录类别	SCIE ; IC
语种	英语
WOS研究方向	Pharmacology & Pharmacy
WOS类目	Chemistry, Medicinal
WOS记录号	WOS:000646195900003
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/126789
专题	生命科学与技术学院_博士生生命科学与技术学院_特聘教授组_李佳组
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
通讯作者单位	上海科技大学
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.
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.
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).