Background:

Ningetinib is a potent, orally bioavailable small molecule tyrosine kinase inhibitor (TKI) with IC50s of 6.7, 1.9 and<1.0 nM for c-Met, VEGFR2 and Axl, respectively.

Ningetinib is a potent, orally bioavailable small molecule tyrosine kinase inhibitor (TKI) with IC50s of 6.7, 1.9 and<1.0 nM for c-Met, VEGFR2 and Axl, respectively. In cell-based functional assays, Ningetinib (CT053PTSA) inhibits HGF and VEGF-stimulated HUVEC proliferation and microvascular angiogenesis in rat aortic rings with IC50 values of 8.6 and 6.3 nM, respectively[1].

When single dosed orally (3 mg/kg) to U87MG tumor-bearing nude mice, Ningetinib (CT053PTSA) potently inhibits the phosphorylation of c-Met and its downstream signaling kinases AKT and ERK1/2 for up to 6 hours in tumor tissues. In orthotopic U87MG human glioblastoma xenograft model, Ningetinib prolongs the median survival time (MST) and yields significant increase in life-span value (ILS=32%, p=0.003) at an oral dose of 20 mg/kg/day (dosed 21 days) versus the vehicle-treated group[1].

参考文献:
[1]. Ning Xi, et al. Abstract 1755: CT053PTSA, a novel c-MET and VEGFR2 inhibitor, potently suppresses angiogenesis and tumor growth. Cancer Res 2014;74(19 Suppl):Abstract nr 1755.