Thalidomide is an inhibitor of angiogenesis.
Thalidomide is a potent teratogen causing dysmelia (stunted limb growth) in humans. We have demonstrated that orally administered thalidomide is an inhibitor of angiogenesis induced by basic fibroblast growth factor in a rabbit cornea micropocket assay. Experiments including the analysis of thalidomide analogs revealed that the antiangiogenic activity correlated with the teratogenicity but not with the sedative or the mild immunosuppressive properties of thalidomide. Electron microscopic examination of the corneal neovascularization of thalidomide-treated rabbits revealed specific ultrastructural changes similar to those seen in the deformed limb bud vasculature of thalidomide-treated embryos. These experiments shed light on the mechanism of thalidomide's teratogenicity and hold promise for the potential use of thalidomide as an orally administered drug for the treatment of many diverse diseases dependent on angiogenesis.
D'Amato
R J
RJ
Department of Surgery, Children's Hospital, Harvard Medical School, Boston 02115.
Loughnan
M S
MS
Flynn
E
E
Folkman
J
J
D000818:Animals; D002642:Chick Embryo; D003315:Cornea; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D066298:In Vitro Techniques; D009389:Neovascularization, Pathologic; D011817:Rabbits; D013792:Thalidomide / Q000494:pharmacology*
D016222:Fibroblast Growth Factor 2; D013792:Thalidomide