Proteolysis-targeting chimera molecules targeting SHP2.

Abstract

SHP2 is a member of the non-receptor protein tyrosine phosphatases, encoded by PTPN11, and exhibits oncogenic activities. The close association between SHP2 and human cancer has made SHP2 a promising target for clinical therapy. Proteolysis-targeting chimera (PROTAC) technology utilizes the degradation mechanism of the ubiquitin proteasome system to degrade specific proteins. It has strong advantages compared with inhibitors. Here we list the four reported PROTAC molecules targeting SHP2 and summarize the recently reported SHP2 inhibitors which can provide lead compounds for designing new SHP2 PROTACs. We also introduce the dual PROTAC technology which may replace drug combinations to treat SHP2-related diseases.