NVP-BHG712 is a specific EphB4 inhibitor with ED50 of 25 nM that discriminates between VEGFR and EphB4 inhibition; also shows activity against c-Raf, c-Src and c-Abl with IC50 of 0.395 μM, 1.266 μM and 1.667 μM, respectively.

c-Src:1.266 μM, C-Raf:0.395 μM, EphB4:25 nM, c-ABL:1.667 μM

In a vascularization model induced by growth factors, NVP-BHG712 (3 mg/kg, p.o) significantly inhibited tissue formation and vascularization stimulated by VEGF through the suppression of EphB4 forward signaling. Additionally, NVP-BHG712 (10 mg/kg, oral administration) effectively reversed the VEGF-enhanced tissue formation and angiogenesis. NVP-BHG712 (3 mg/kg, orally) exhibited a sustained exposure in mouse plasma as well as lung and liver tissues for up to 8 hours at approximately 10 μM concentration, thereby resulting in long-lasting inhibition of EphB4 kinase activity.

NVP-BHG712 exhibits dose-dependent inhibition of RTK autophosphorylation in A375 melanoma cells stably transfected, with EC50 values of 25 nM for EphB4 and 4.2 μM for VEGFR2.