Ningetinib

Ningetinib (CT053PTSA) is an orally bioavailable tyrosine kinase inhibitor with IC50s of <1.0, 1.9 and 6.7 nM for Axl, VEGFR2, and c-Met, respectively.In cell-based functional assays, Ningetinib inhibits VEGF and HGF-stimulated HUVEC proliferation and microvascular angiogenesis in rat aortic rings with IC50 values of 6.3 and 8.6 nM, respectively.In the orthotopic U87MG human glioblastoma xenograft model, Ningetinib prolongs the median survival time and yields a significant increase in life-span value (ILS=32%) at an oral dose of 20 mg/kg/day (dosed 21 days) versus the vehicle-treated group. When single dosed orally (3 mg/kg) to U87MG tumor-bearing nude mice, Ningetinib potently inhibits the phosphorylation of c-Met and its downstream signaling kinases AKT and ERK1/2 for up to 6 hours in tumor tissues.