EVT801 is a highly selective and low-toxic VEGFR-3 inhibitor that inhibits VEGF-C-induced tumor lymphoid and angiogenesis and reduces important circulating immunosuppressive factors (CCL4, CCL5) and myeloid-derived suppressor cells (MDSC).

VEGFR2:130 nM, VEGFR3:11 nM, VEGFR1:396 nM, ERK:13 nM

In HEK293 cells, EVT801 (10 nM–1 μM) dose-dependently inhibited autophosphorylation of VEGFR-1/2/3, with IC₅₀ values of 2130 nM (VEGFR-1), 260 nM (VEGFR-2), and 39 nM (VEGFR-3) [1]. In human lymphatic microvascular endothelial cells (hLMVECs), EVT801 (1 nM–1 μM) inhibited proliferation induced by VEGF-C, VEGF-D, and VEGF-A with IC₅₀ values of 15 nM, 8 nM, and 155 nM, respectively [1]. EVT801 (1 μM; 72 h) also suppressed proliferation of VEGFR-3–positive tumor cells in vitro [1].

EVT801 (30 mg/kg; oral administration; twice daily for 7 days) has demonstrated antitumor effects in various VEGFR-3–positive mouse tumor models, including the RT-001-HAM subcutaneous patient-derived xenograft (PDX) model, the 4T1 mammary carcinoma model, the N-diethylnitrosamine-induced hepatocarcinoma model, the NCI-H1703 subcutaneous xenograft model, the Rip1-Tag2 transgenic model, and the CT26 ectopic tumor model. VEGFR-3 expression was observed in tumor-associated blood vessels in primary and metastatic kidney cancers, as well as in endothelial tumor cells. [1]