Abstract
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 PDGFRβ (platelet-derived growth factor receptor β). GS-493 also inhibits purified human PDGFRβ and SRC in vitro, whereas PDGFRβ 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.
Original language | English |
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Pages (from-to) | 1405-1411 |
Number of pages | 7 |
Journal | FEBS Open Bio |
Volume | 8 |
Issue number | 9 |
DOIs | |
Publication status | Published - 2018 Sep |
Keywords
- 11a-1
- GS-493
- IIB-08
- NSC-87877
- PDGFRβ
- SHP2 inhibitor
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)