AZD2932 is a new series of quinazoline ether inhibitor which potently inhibits VEGFR-2 and PDGFR with IC50s of 4 nM/8 nM/ 7 nM for PDGFRβ/VEGFR-2/Flt-3.

The same C6 in vivo model was used to study tumor growth inhibition (TGI) with AZD2932. Twice daily oral dosing (b.i.d.) 10 h apart resulted in significant TGI of 64% for both 50 and 12.5 mg/kg doses on the day the control animals were terminated (day 22 on the graph). Most importantly, xenografts bearing non-PDGFR expressing tumor cells were also sensitive to AZD2932 treatment: growth of Calu-6 tumor was inhibited by 81% and 72% at 50 and 12.5 mg/kg b.i.d. (p <0.001) and LoVo tumors by 67% at 50 mg/kg b.i.d. (p <0.001).

AZD-2932 is a high affinity inhibitor of VEFGR-2 and PDGFR. AZD-2932 has a balanced  ~1:1 ratio of activity vs both VEGFR-2 and PDGFRβ and shows IC50 values of 8 and 4 nM against the two enzymes, respectively. It is also active on c-Kit and FLT3 with good selectivity on a panel of kinases. The pharmacokinetic behavior and the preclinical antitumor activity in nude mice bearing C6 rat glial tumors indicate that 31 has the potential to become an antiangiogenic agent in the clinic.