Pamufetinib mesylate (TAS-115 mesylate) is a potent vascular endothelial growth factor receptor (VEGFR) antagonist and hepatocyte growth factor receptor (c-Met) inhibitor used in the study of cancer and respiratory diseases.

MET (rat):39 nM (Ki), VEGFR2 (rat):12 nM (Ki)

Pamufetinib mesylate is an ATP antagonist with inhibition constants (Ki) of 12 nM and 39 nM for rVEGFR2 and rMET, respectively.It potently inhibits the kinase activity of VEGFR2 and MET and their signaling-dependent cellular growth, with effects comparable to other known VEGFR or MET inhibitors. In addition, Pamufetinib mesylate caused less damage to a variety of normal cells than other VEGFR inhibitors.
At concentrations below 10 μM, Pamufetinib mesylate did not affect the growth of PC-9 or HCC827 cells, but was able to concentration-dependently reverse HGF-induced resistance in both cell lines when combined with erlotinib. In addition, Pamufetinib mesylate inhibits VEGF production and endothelial cell proliferation in cancer cells. [1][2]

Pamufetinib mesylate (50 mg/kg/d) was able to completely inhibit tumor growth during treatment. And in a MET-amplified human cancer transplant model, Pamufetinib mesylate (200 mg/kg/d) regressed tumor volume by 48% from the initial volume. In this model, the 50% effective dose (ED50) of Pamufetinib was estimated to be 8 mg/kg/d. Pamufetinib mesylate significantly prolonged survival in mice when administered at doses of 50 or 200 mg/kg/d. Meanwhile, Pamufetinib mesylate effectively inhibited angiogenesis in the PC-9/HGF tumor model. In addition, the combination of erlotinib and Pamufetinib mesylate successfully inhibited PC-9/HGF tumor growth and delayed tumor regeneration that was still associated with persistent vasculature inhibition even after cessation of treatment. [1][2]