A-357300

A-357300 is a reversible and selective MetAP2 inhibitor with IC₅₀s of 0.12 and 57 μM against MetAP2 and MetAP1. A-357300 induces cytostasis by cell cycle arrest at the G1 phase selectively in endothelial cells and in a subset of tumor cells. A-357300 inhibits angiogenesis both in vitro and in vivo and shows potent antitumor efficacy in carcinoma, sarcoma, and neuroblastoma murine models. A-357300 can be used for the studies of neuroblastoma, fibrosarcoma and breast cancer^[1]. In Vitro:A-357300 (0.1 nM-100 μM, 3 days) exhibits selective antiproliferative activity against endothelial cells and tumor cells with IC₅₀s of 0.1-2 μM, but not in human primary cells^[1].
A-357300 (10 μM, 3 days) induces cytostasis by cell cycle arrest at the G1 phase in HMVECs or HT-1080 cells^[1].
A-357300 (0-10 μM, 1 day) reduces the concentration of cyclin A, while keeping the concentration of cyclin D1 unchanged in HMVECs^[1].
A-357300 (0.08-2 μM, 3 days) completely blocks the formation of the lumen at a concentration of 0.4 μM in HMVECs^[1].
In Vivo:A-357300 (25-100 mg/kg, s.c., twice daily for 7 days) shows inhibition of mouse cornea angiogenesis^[1].
A-357300 (8-100 mg/kg, s.c., once every other day or twice daily for 14-24 days) inhibits the growth of neuroblastoma, fibrosarcoma and breast cancer in mice^[1].