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SOMCL-085, a Novel Multi-Targeted FGFR Inhibitor, Displays Potent Anticancer Activity in FGFR-addicted Human Cancer Models

SOMCL-085, a Novel Multi-Targeted FGFR Inhibitor, Displays Potent Anticancer Activity in FGFR-addicted Human Cancer Models

Xi-Fei Jiang, Yang Dai, Xia Peng, Yan-Yan Shen, Yi Su, Man-Man Wei, Wei-Ren Liu, Zhen-Bin Ding, Ao Zhang, Ying-Hong Shi, Jing Ai

Acta Pharmacol Sin. 2018 Feb;39(2):243-250.

PMID: 28905937

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 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 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 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP192705796-A	FGF Receptor Tyrosine Kinase Inhibitor - CAS 192705-79-6		192705-79-6	Price

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