Journal
FEBS OPEN BIO
Volume 8, Issue 9, Pages 1405-1411Publisher
WILEY
DOI: 10.1002/2211-5463.12493
Keywords
11a-1; GS-493; IIB-08; NSC-87877; PDGFR beta; SHP2 inhibitor
Categories
Funding
- NIH [R37CA49132]
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Due to the involvement of SHP2 (SH2 domain-containing protein-tyrosine phosphatase) in human disease, including Noonan syndrome and cancer, several inhibitors targeting SHP2 have been developed. Here, we report that the commonly used SHP2 inhibitor NSC-87877 does not exhibit robust inhibitory effects on growth factor-dependent MAPK (mitogen-activated protein kinase) pathway activation and that the recently developed active site-targeting SHP2 inhibitors IIB-08, 11a-1, and GS-493 show off-target effects on ligand-evoked activation/trans-phosphorylation of the PDGFR (platelet-derived growth factor receptor ). GS-493 also inhibits purified human PDGFR and SRC in vitro, whereas PDGFR inhibition by IIB-08 and 11a-1 occurs only in the cellular context. Our results argue for extreme caution in inferring specific functions for SHP2 based on studies using these inhibitors.
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