o-(chloroacetylcarbamoyl)fumagillol and 6-amino-5-bromouracil

7-Deazaxanthine (7DX) was identified as a novel inhibitor of thymidine (dThd) phosphorylase (TPase). It inhibited the TPase reaction in a concentration-dependent manner. At 1 mM, it almost completely prevented the TPase-catalysed hydrolysis of dThd to thymine. The 50% inhibitory concentration (IC50 of 7DX was 40 microM in the presence of 100 microM of the natural substrate dThd. 7DX is also endowed with a marked inhibitory effect on angiogenesis. It significantly prevents neovascularisation in the chicken chorioallantoic membrane during development. 7DX is the first purine derivative shown to be a potent inhibitor of purified TPase and angiogenesis.

Topics: Allantois; Animals; Antibiotics, Antineoplastic; Binding Sites; Bromouracil; Chick Embryo; Chorion; Cyclohexanes; Dose-Response Relationship, Drug; Drug Design; Enzyme Inhibitors; Escherichia coli; Neovascularization, Physiologic; O-(Chloroacetylcarbamoyl)fumagillol; Sesquiterpenes; Thymidine; Thymidine Phosphorylase; Thymine; Xanthines