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.

Type

Journal article

Journal

FEBS Lett

Publication Date

30/10/1998

Volume

438

Pages

91 - 95

Keywords

Allantois, Animals, Antibiotics, Antineoplastic, Binding Sites, Bromouracil, Chick Embryo, Chorion, Cyclohexanes, Dose-Response Relationship, Drug, Drug Design, Enzyme Inhibitors, Escherichia coli, Neovascularization, Physiologic, Sesquiterpenes, Thymidine, Thymidine Phosphorylase, Thymine, Xanthines