文献类型：期刊文献

英文题名：Therapeutic potential of targeting SHP2 in human developmental disorders and cancers

作者：Shen, Dadong[1];Chen, Wenxia[2];Zhu, Jinlin[2];Wu, Guofeng[2];Shen, Runpu[3];Xi, Meiyang[3];Sun, Haopeng[4]

机构：[1]Zhejiang Univ Technol, Coll Pharmaceut Sci, Hangzhou 310014, Peoples R China;[2]Zhejiang Med Co Ltd, Res & Dev Ctr, Shaoxing 312500, Peoples R China;[3]Shaoxing Univ, Coll Chem & Chem Engn, Shaoxing 312000, Peoples R China;[4]China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Peoples R China

年份：2020

卷号：190

外文期刊名：EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

收录：SCI-EXPANDED(收录号：WOS:000518870100002)、、Scopus(收录号：2-s2.0-85079172762)、WOS

基金：The authors acknowledge the grants of National Natural Science Foundation of China (No. 81573281, 81602949) and the support from the Science Foundation of Shaoxing University (No. 20175022, 2018LG1001).

语种：英文

外文关键词：Developmental disorder; Cancer; SHP2 inhibitor; Catalytic pocket; Allosteric site

外文摘要：Src homology 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11, regulates cell proliferation, differentiation, apoptosis and survival via releasing intramolecular autoinhibition and modulating various signaling pathways, such as mitogen-activated protein kinase (MAPK) pathway. Mutations and aberrant expression of SHP2 are implicated in human developmental disorders, leukemias and several solid tumors. As an oncoprotein in some cancers, SHP2 represents a rational target for inhibitors to interfere. Nevertheless, its tumor suppressive effect has also been uncovered, indicating the context-specificity. Even so, two types of SHP2 inhibitors including targeting catalytic pocket and allosteric sites have been developed associated with resolved cocrystal complexes. Herein, we describe its structure, biological function, deregulation in human diseases and summarize recent advance in development of SHP2 inhibitors, trying to give an insight into the therapeutic potential in future. (C) 2020 Elsevier Masson SAS. All rights reserved.