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Aberrant fibroblast growth factor receptor (FGFR) activation is found across a diverse spectrum of malignancies,especially those lacking effective treatments.SOMCL-085 is a novel FGFR-dominant multi-target kinase inhibitor.Here,we explored the FGFR-targeting anticancer activity of SOMCL-085 both in vitro and in vivo.Among a panel of 20 tyrosine kinases screened,SOMCL-085 potently inhibited FGFR1,FGFR2 and FGFR3 kinase activity,with IC50 values of 1.8,1.9 and 6.9 nmol/L,respectively.This compound simultaneously inhibited the angiogenesis kinases VEGFR and PDGFR,but without obvious inhibitory effect on other 12 tyrosine kinases.In 3 representative human cancer cell lines with different mechanisms of FGFR activation tested,SOMCL-085 (20-500 nmol/L) dose-dependently inhibited FGFR1-3 phosphorylation and the phosphorylation of their key downstream effectors PLCy and Erk.In 7 FGFR aberrant human cancer cell lines,regardless of the mechanistic complexity of FGFR over-activation,SOMCL-085 potently inhibited FGFR-driven cell proliferation by arresting cells at the G1/S phase.In the FGFR1-amplified lung cancer cell line H1581 xenograft mice and FGFR2-amplified gastric cancer cell line SNU16 xenograft mice,oral administration of SOMCL-085 (25,50 mg·kg-1·d-1) for 21 days substantially suppressed tumor growth without affecting their body-weight.These results suggest that SOMCL-085 is a potent multi-target FGFR inhibitor that inhibits the FGFR-dependent neoplastic phenotypes of human cancer cells in vitro and in vivo.