OSI-930

OSI-930 is an orally selective inhibitor of Kit, KDR and CSF-1R (c-Fms) with IC₅₀s of 80 nM, 9 nM and 15 nM, respectively. OSI-930 also moderately inhibits Flt-1, c-Raf, Lck and low activity against PDGFRα/β, Flt-3 and Abl. OSI-930 has antitumor activity^[1]. In Vitro: OSI-930 inhibits cell proliferation in the HMC-1 cell line with IC₅₀ of 14 nM but has no significant effect on the growth of COLO-205 cell line that does not express constitutively active mutant receptor tyrosine kinase^[1]. OSI-930 induces apoptosis in HMC-1 cell line with an EC₅₀ value of 34 nM^[1]. OSI-930 inactivates purified, recombinant cytochrome P450 3A4 with a K_i of 24 μM in a time- and concentration-dependent manner^[2] In Vivo: OSI-930 (oral gavage; once a day; 38 days; 200 mg/kg) exhibits potent antitumor activity in a broad range of preclinical xenograft models^[1].