Anti-angiogenic activity of a novel synthetic agent, 9 alpha-fluoromedroxyprogesterone acetate

9 alpha-Fluoromedroxyprogesterone acetate (FMPA) is a novel synthetic analo g of medroxyprogesterone acetate (MPA), widely used as therapeutic agent fo r breast and endometrium cancers, FMPA showed almost the same binding affin ities to the progesterone and glucocorticoid receptors as MPA. In the rabbi t corneal assay, FMPA, MPA and fumagillin significantly inhibited the angio genic response induced by rat mammary tumor at doses of 0.1, 1 and 50 mu g/ pellet, respectively, so FMPA showed greater anti-angiogenic activity than MPA and fumagillin. In the mouse dorsal air sac method, FMPA inhibited the mouse sarcoma 180 cell-induced angiogenesis by oral administration at a dos e of 200 mg/kg. FMPA inhibited the activity of plasminogen activator (PA) i n bovine endothelial cells. These results suggest that FMPA may be useful f or diseases associated with angiogenesis by oral administration. (C) 1999 E lsevier Science Ireland Ltd. All rights reserved.