Pamufetinib (TAS-115) is a potent inhibitor of VEGFR and hepatocyte growth factor receptor (c-Met/HGFR)-targeted kinase(IC50s of 30 and 32 nM for rVEGFR2 and rMET, respectively).

pamufetinib is ATP antagonism(Ki of 12 and 39 nM for rVEGFR2 and rMET, respectively). Like other known VEGFR or MET inhibitors, AS-115 strongly inhibits the kinase activity of VEGFR2 and MET and their signal-dependent cell growth. TAS-115 induces less damage in various normal cells than do other VEGFR inhibitors[1]. TAS-115 does not affect the growth of PC-9 or HCC827 cells at concentrations less than 10 μM; however, the combined use of TAS-115 with erlotinib reverses HGF-induced resistance in the cell lines in a concentration-dependent manner. VEGF production by cancer cells and endothelial proliferation inhibited by TAS-115[2].

During the treatment period,pamufetinib (50 mg/kg/d) completely prevents tumor growth. In MET-amplified human cancer transplanted models,pamufetinib (200 mg/kg/d) induces a 48% regression from the initial tumor volume . ED50 of Tpamufetinib in this model is 8 mg/kg/d. Pamufetinib significantly prolongs survival of these mice when administered at doses of 50 or 200 mg/kg/d[1]. Pamufetinib inhibits angiogenesis in PC-9/HGF tumors in vivo. Moreover, the doublet erlotinib and pamufetinib successfully inhibit PC-9/HGF tumor growth and delay tumor regrowth associated with sustained tumor vasculature inhibition even after cessation of the treatment[2].