In aged mouse model, hepatocyte-specific deletion of PTPN11/Shp2 promotes inflammatory signaling through the STAT3 pathway and hepatic inflammation/necrosis, resulting in regenerative hyperplasia and spontaneous development of tumors.

SHP2 is now considered as a compelling anticancer drug target and several classes of SHP2 inhibitors with different mode of action are developed with some already in clinical trial phases. Moreover, novel SHP2 substrates and functions are rapidly growing both in cell and cancer.

Oct 22, 2020 · To date, four SHP2 allosteric inhibitors have entered clinical trials for the treatment of solid tumors. This review will provide a summary of the physiological and biological functions of SHP2 and discuss the development of nonallosteric/allosteric SHP2 inhibitors in recent years.

Oct 8, 2020 · SH2 containing protein tyrosine phosphatase-2 (SHP2) is an oncogenic phosphatase known to facilitate growth and survival signaling downstream of numerous receptor inputs. Herein, we used...

Apr 15, 2021 · Inhibitors of SHP2, an important regulator of RAS-MAPK signaling, are being tested in human trials to make other cancer drugs more effective.

Jan 4, 2023 · In this chapter, we comprehensively summarize the multifaceted functions of SHP2 and the structural basis of SHP2 under different conditions. Additionally, the challenges and prospects of SHP2-targeted drug discovery are also discussed.

Dec 1, 2000 · SHP-2, a cytoplasmic SH2 domain containing protein tyrosine phosphatase, is involved in the signaling pathways of a variety of growth factors and cytokines.