TAS 115 is a multi-kinase inhibitor that inhibits the growth factor receptors PDGFRα and PDGFRβ (IC50s = 0.81 and 7.06 nM, respectively), c-FMS (IC50 = 15 nM), VEGFR2 and VEGFR1 (IC50s = 30 and 140 nM, respectively), Met (IC50 = 32 nM), and FGFR2 (IC50 = 340 nM).1,2 It also inhibits Axl, c-Kit, Src, and FLT1.1 TAS 115 inhibits VEGF-induced VEGFR2 phosphorylation in human umbilical vein endothelial cells (HUVECs) and Met phosphorylation in Met-amplified MKN45 human gastric cancer cells. It also inhibits VEGF-dependent, but not VEGF-independent, growth of HUVECs (IC50s = 0.019 and 19.3 ?M, respectively) and of Met-amplified MKN45, but not Met-inactivated, human MCF-7 breast cancer cells (GI50s = 0.032 and >10 ?M, respectively). TAS 115 reduces tumor growth in a MKN45 mouse xenograft model (ED50 = 8 mg/kg).
1.Fujita, H., Miyadera, K., Kato, M., et al.The novel VEGF receptor/MET-targeted kinase inhibitor TAS-115 has marked in vivo antitumor properties and a favorable tolerability profileMol. Cancer Ther.12(12)2685-2696(2013) 2.Koyama, K., Goto, H., Morizumi, S., et al.The tyrosine kinase inhibitor TAS-115 attenuates bleomycin-induced lung fibrosis in miceAm. J. Respir. Cell Mol. Biol.60(4)478-487(2019)