AZD2932

AZD2932 is a potent and multi-targeted kinase inhibitor VEGFR2, PDGFβ, Flt-3 and c-Kit with IC₅₀s of 8, 4, 7 and 9 nM in cell assay, respectively. IC50 & Target: IC50: 8 nM (VEGFR2), 4 nM (PDGFβ), 7 nM (Flt-3), 9 nM (c-Kit)^[1] In Vitro: AZD2932 has a potent and balanced profile against PDGFβ, VEGFR-2, Flt-3 and c-Kit. It does not inhibit the various cytochrome P450 isoforms with the worst IC₅₀ being against 2C9 (8.0 μM). AZD2932 has no activity against hERG (IC₅₀=137 μM)^[1]. In Vivo: Twice daily oral dosing (b.i.d.) of AZD2932 10 h apart results in significant tumor growth inhibition of 64% for both 50 and 12.5 mg/kg doses on the day the control animals are terminated. Xenografts bearing non PDGFβ expressing tumor cells are also sensitive to AZD2932 treatment: growth of Calu-6 tumor is inhibited by 81% and 72% at 50 and 12.5 mg/kg b.i.d. and and LoVo tumors by 67% at 50 mg/kg b.i.d. This is due AZD2932 potent activity against VEGFR2 as well as a potential effect on pericytes and tumor-associated fibroblasts due to PDGFR a and b inhibition. AZD2932 at 3–50 mg/kg b.i.d. 10 h apart gives 60–80% inhibition of both p-VEGFR2 and p-PDGFβ in a 1:1 ratio^[1].