%0 Journal Article %T SOMCL-085, a novel multi-targeted FGFR inhibitor, displays potent anticancer activity in FGFR-addicted human cancer models %A JIANG Xi-fei %A DAI Yang %A PENG Xia %A SHEN Yan-yan %A SU Yi %A WEI Man-man %A LIU Wei-ren %A DING Zhen-bin %A ZHANG Ao %A SHI Ying-hong %A AI Jing %J Acta Pharmacologica Sinica %D 2018 %B 2018 %9 %! SOMCL-085, a novel multi-targeted FGFR inhibitor, displays potent anticancer activity in FGFR-addicted human cancer models %K %X Abstract 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 FGFRtargeting 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 IC 50 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 PLCγ 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 G 1 /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 . %U http://www.chinaphar.com/article/view/9723 %V 39 %N 2 %P 243-250 %@ 1745-7254