Potent inhibition of angiogenesis by wortmannin, a fungal metabolite.

Wortmannin ([1S-(1 alpha, 6b alpha, 9a beta, 11 alpha, 11b beta)]-11-(acetyloxy)-1,6b,7,8,9a,10,11,11b-octahydro-1- (methoxymethyl)-9a, 11b-dimethyl-3 H-furo[4,3,2-de]indeno[4,5-h]-2-benzopyran-3,6,9-trione), a fungal metabolite that is as a selective inhibitor of phosphatidylinositol 3-kinase, was evaluated for its potential as an inhibitor of in vivo angiogenesis in a bioassay system involving growing chick embryo chorioallantoic membranes. It showed dose-dependent inhibitory activity against embryonic angiogenesis. This inhibition occurred at a dose as low as 1 ng (2.3 pmol) per egg and the ID50 value was 30 ng/egg. These findings suggest that wortmannin is a new angiogenesis inhibitor, and that it may be a lead antibiotic for a novel class of therapeutic agents for angiogenesis-dependent diseases like cancer, diabetic retinopathy and rheumatoid arthritis.