Abstract
Wortmannin ([1 S-(1α,6 bα,9 aβ,11α,11 bβ)]-11-(acetyloxy)-1,6 b,7,8,9 a,10,11,11 b-octahydro-1-(methoxymethyl)-9 a,11 b-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 ID 50 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.
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