BMS-794833,a potent ATPcompetitive Met/VEGFR-2 kinase inhibitor,demonstrates enhanced activity versus both Met-dependent and Met-insensitive tumor lines. BMS-794833 also inhibits Ron (Met family),Axl (phylogenetically related Axl/Tyro3/Mer subfamily) and Flt-3 with IC50 values <3 nM. The compound was selective versus a panel of >200 additional RTKs, non-RTKs and serine/threonine kinases based on biochemical or Ambit binding assays. In cell culture, BMS-794833 inhibited the proliferation of human tumor cell lines containing constitutively activated Met receptor (GTL-16 gastric carcinoma). Tumor cell lines whose growth is stimulated by HGF (U87 glioblastoma) were also effectively inhibited by BMS-794833. In vivo, BMS-794833 demonstrated dose-dependent tumor growth inhibition following oral administration in the GTL-16 and L2987 lung carcinoma (Met-insensitive) xenograft models. Despite the impressive antitumor activity, BMS-794833 showed dissolution rate-limited absorption from solid dosage forms.