EVT801 (EVT 801) is a potent, selective VEGFR-3 inhibitor with biochemical IC50 of 11 nM, inhibits cellular VEGFR-3 autophosphorylation with IC50 of 39 nM.
EVT801 displays 30-fold and 50-fold selectivity over VEGFR-2 and VEGFR-1 in cellular assays, respectively.
EVT801 potently inhibits VEGFR-3 autophosphorylation in various mammalian species, with an IC50 in cellular assays ranging from 151 nM for the mouse receptor to 32 nM for the monkey protein.
EVT801 undergoes O-demethylation in the cell, giving rise to the active metabolite SAR401849, which is as potent and selective as EVT801.
EVT801 strongly inhibited VEGF-C–induced ERK1/2 phosphorylation with an IC50 of 13 nM in hLMVECs.
EVT801 inhibited the induction of hLMVEC proliferation in a dose-dependent manner with an IC50 of 15 nmol/L for VEGF-C, 8 nmol/L for VEGF-D, and 155 nmol/L for VEGF-A, and a maximum inhibition of 74%, 100%, and 65%, respectively.
EVT801 reduced ERK phosphorylation induced by VEGF-C and VEGF-D better than pazopanib in NCI-H1703 cells.
EVT801(30 mg/kg twice per day, oral) showed a significant inhibition of tumor growth in NCI-H1703 tumor xenografts, blocked hypoxia-driven immunosuppression and enhances ICT efficacy.