The EphB4 receptor tyrosine kinase (cloned from erythropoietin-producing hepatocellular carcinoma) and its ligand ephrinB2 play an important role in embryonic vessel development and vascular remodeling. Signaling from this pair is also involved in tumor angiogenesis. NVP-BHG712 is an orally bioavailable inhibitor of EphB4 kinase autophosphorylation (ED50 = 25 nM). It is selective for EphB4, demonstrating an ED50 value of 4.2 μM at the related VEGFR2 receptor and ED50 values >10 μM against a panel of 40 additional kinases. At 3-30 mg/kg, NVP-BHG712 dose dependently inhibits VEGF-directed vessel formation in an in vivo mouse model of angiogenesis.