We developed an oral administration-compatible, small molecular weight antitumor agent, YM-201627 by screening for the inhibition of the proliferation of VEGF-stimulated HUVECs. YM-201627 selectively inhibited the proliferation of various endothelial cell lines induced by VEGF, bFGF, and FBS (at IC 50 s of 0.0039–0.12 μM), that would not be expected to have any direct antiproliferative effect on other cell types. YM-201627 inhibited angiogenesis in vitro at a concentration of 0.01 μM. In the in vivo studies, it inhibited microvessel formation induced by human melanoma A375 cells suspended in Matrigel (86% with twice-daily doses of 30 mg/kg). Moreover, once-daily oral dosing of YM-201627 to mice bearing A375 xenografts elicited significant antitumor activity (73% with daily doses of 10 mg/kg). These results suggest that YM-201627 is a selective growth inhibitor of endothelial cells, which may be useful for treatment of solid tumors.