Pamufetinib (mesylate)

Pamufetinib (TAS-115) mesylate is a potent VEGFRand hepatocyte growth factor receptor (c-Met/HGFR)-targeted kinase inhibitor, with IC₅₀s of 30 and 32 nM for rVEGFR2 and rMET, respectively. IC50 & Target: IC50: 30 nM (rVEGFR2), 32 nM (rMET)^[1] In Vitro: Pamufetinib mesylate powerfully suppresses the VEGF-dependent proliferation of HUVECs (IC₅₀=0.019 μM) as a VEGFR-targeted inhibitor and powerfully suppresses the proliferation of MET-amplified cancer cells (GI₅₀=0.032-0.362 μM) as a MET-targeted inhibitor. Pamufetinib mesylate has much less toxicity in various normal cell lines when compared with other VEGFR-targeted kinase inhibitors^[1]. Crizotinib and Pamufetinib mesylate inhibit Met phosphorylation and reverse erlotinib resistance and VEGF production triggered by HGF in PC-9 and HCC827 cells^[2]. In Vivo: Pamufetinib mesylate completely suppresses the progression of MET-inactivated tumor by blocking angiogenesis without toxicity when given every day for 6 weeks, even at a serum-saturating dose of Pamufetinib mesylate. Pamufetinib mesylate induces marked tumor shrinkage and prolonges survival in MET-amplified human cancer–bearing mice^[1].