Novel PROTACs for degradation of SHP2 protein

被引：46

作者：

Zheng, Mengzhu ^{[1
]}

Liu, Yang ^{[2
]}

Wu, Canrong ^{[1
]}

Yang, Kaiyin ^{[1
]}

Wang, Qiqi ^{[2
]}

Zhou, Yirong ^{[1
]}

Chen, Lixia ^{[2
]}

Li, Hua ^{[1
,2
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Pharm, Hubei Key Lab Nat Med Chem & Resource Evaluat, Wuhan 430030, Peoples R China

[2] Shenyang Pharmaceut Univ, Key Lab Struct Based Drug Design & Discovery, Dept Nat Prod Chem, Sch Tradit Chinese Mat Med,Minist Educ, Shenyang 110016, Peoples R China

来源：

BIOORGANIC CHEMISTRY | 2021年 / 110卷

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

SHP2; PROTAC; Protein degrader; TYROSINE PHOSPHATASES; INHIBITOR; DOMAIN;

D O I：

10.1016/j.bioorg.2021.104788

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Protein tyrosine phosphatase SHP2 is a member of PTPs family associated with cancer such as leukemia, nonsmall cell lung cancer, breast cancer, and so on. SHP2 is a promising target for drug development, and consequently it is of great significance to develop SHP2 inhibitors. Herein, we report CRBN-recruiting PROTAC molecules targeting SHP2 by connecting pomalidomide with SHP099, an allosteric inhibitor of SHP2. Among them, SP4 significantly inhibited the growth of Hela cells, compared with SHP099, its activity increased 100 times. In addition, it can significantly induce SHP2 degradation and cell apoptosis. Further study of SHP2-protac may have important significance for the treatment of SHP2 related diseases.

引用

页数：8

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