Ningetinib

• CAT Number: I012948
• CAS Number: 1394820-69-9
• Molecular Formula: C31H29FN4O5
• Molecular Weight: 556.58
• Purity: ≥95%
• Synonyms: N-[3-fluoro-4-[7-(2-hydroxy-2-methylpropoxy)quinolin-4-yl]oxyphenyl]-1,5-dimethyl-3-oxo-2-phenylpyrazole-4-carboxamide
• InChI: InChI=1S/C31H29FN4O5/c1-19-28(30(38)36(35(19)4)21-8-6-5-7-9-21)29(37)34-20-10-13-27(24(32)16-20)41-26-14-15-33-25-17-22(11-12-23(25)26)40-18-31(2,3)39/h5-17,39H,18H2,1-4H3,(H,34,37)
• InChIKey: VQYYQSZNRVQLIS-UHFFFAOYSA-N
• SMILES: CC1=C(C(=O)N(N1C)C2=CC=CC=C2)C(=O)NC3=CC(=C(C=C3)OC4=C5C=CC(=CC5=NC=C4)OCC(C)(C)O)F

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].

Reference

[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.