Chiauranib is a multi-target inhibitor against tumor angiogenesis and exhibits potent anticancer effects. Chiauranib potently inhibits the angiogenesis-related kinases (VEGFR1, VEGFR2, VEGFR3, PDGFRα and c-Kit), mitosis-related kinase Aurora B, and chronic inflammation-related kinase CSF1R, with IC50 values ranging from 1-9 nM.

Aurora B:9 nM, KDR:7 nM, PDGFRβ:93 nM, FLK1:8 nM, CSF1R:7 nM, FLT4:9 nM, c-Kit:4 nM, PDGFRα:1 nM

In HUVEC and PDGFRβ phosphorylation in PDGFRβ overexpressed NIH3T3 cells, Chiauranib (CS2164; 0.03-3 μM) suppressed VEGFR/PDGFR phosphorylation, inhibited ligand-dependent cell proliferation, and capillary tube formation, and prevented vasculature formation in tumor tissues. Chiauranib (CS2164) inhibited CSF-1R phosphorylation that lead to the suppression of ligand-stimulated monocyte-to-macrophage differentiation and reduced CSF-1R+ cells in tumor tissues. Chiauranib (3 μM; 24 hours) showed induction of G2/M cell cycle arrest and suppression of cell proliferation in tumor tissues through the inhibition of Aurora B-mediated H3 phosphorylation[1].

Chiauranib exhibited broad and potent anti-tumor activities in vivo. Chiauranib (2.5 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg, 40 mg/kg; oral) induced remarkable regression or complete inhibition of tumor growth at well-tolerated oral doses in several human tumor xenograft models[1].