A-357300 is a potent, selective, reversible MetAP2 inhibitor with IC50 of 0.12 uM, does not inhibit MetAP1 or leucine aminopeptidases at 10 uM.
A-357300 suppresses tumor growth preclinically without the toxicities observed with TNP-470, induces cytostasis by cell cycle arrest at the G(1) phase selectively in endothelial cells and in a subset of tumor cells, but not in most primary cells of nonendothelial type.
A-357300 inhibits angiogenesis both in vitro and in vivo and shows potent antitumor efficacy in carcinoma, sarcoma, and neuroblastoma murine models.
