MGCD-265

MGCD-265 is a potent, multi-target and ATP-competitive inhibitor of c-Met and VEGFR1/2/3 with IC50 of 1 nM, 3 nM/3 nM/4 nM, respectively; also inhibits Ron and Tie2. Phase 1/2. (In Vitro) :MGCD-265 analog inhibits A549 cells migration and DU145 cells scattering, with IC50s of 0.4 μM and 0.08 μM, respectively, in HGF-driven cell migration and scattering assays.MGCD-265 analog inhibits HUVEC ERK phosphorylation (IC50=0.03 μM) and HUVEC proliferation (IC50=0.006 μM) in VEGF-dependent cell-based assays. (In Vivo) :MGCD-265 analog (20 mg/kg; p.o.) inhibits tumor growth inhibition on various human tumor models in mice.MGCD-265 analog exhibits moderate oral bioavailability (rat 12%, dog 42%) and Cmax (rat 0.14, dog 0.21 uM/ (mg/kg) ) following oral administration (rat 5-25, dog 5 mg/kg) .MGCD-265 analog exhibits reasonable terminal elimination half-lives (rat 1.2, dog 5.8 h) due to plasma clearance (rat 0.33, dog 1.1 L/ (kg h) ) following intravenous administration (rat 2.5, dog 0.8 mg/kg) .