Tyrosine phosphatase SHP2 inhibitors in tumor-targeted therapies

Src homology containing protein tyrosine phosphatase 2(SHP2)represents a noteworthy target for various diseases,serving as a well-known oncogenic phosphatase in cancers.As a result of the low cell permeability and poor bioavailability,the traditional inhibitors targeting the protein tyrosine phosphate catalytic sites are generally suffered from unsatisfactory applied efficacy.Recently,a particularly large number of allosteric inhibitors with striking inhibitory potency on SHP2 have been identified.In particular,few clinical trials conducted have made significant progress on solid tumors by using SHP2 allosteric inhibitors.This review summarizes the development and structureeactivity relationship studies of the small-molecule SHP2 inhibitors for tumor therapies,with the purpose of assisting the future development of SHP2 inhibitors with improved selectivity,higher oral bioavailability and better physicochemical properties.