The efficient inhibition of angiogenesis is considered as a promising strategy for the treatment of angiogenesis-related diseases including cancer. Herein, we report that embellistatin, a bicyclic ketone compound known as a microtubule polymerization inhibitor, exhibits anti-angiogenic activity. Embellistatin inhibited in vitro angiogenesis of bovine aortic endothelial cells (BAECs) such as bFGF-induced invasion and tube formation as well as bFGF-induced mouse corneal angiogenesis in vivo. Notably, embellistatin exhibited stronger inhibition activity for the growth of BAECs than that of normal and cancer cell lines. Cell cycle analysis revealed that the compound arrests cell cycle at G(2)/M phase, which is associated with the increased expression of p21(WAF1) and p53 partly. These results demonstrate that embellistatin may serve the basis for the development of new anti-angiogenic agents. (c) 2006 Elsevier Inc. All rights reserved.