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.

Original publication

DOI

10.1016/s0014-5793(98)01271-x

Type

Journal article

Journal

FEBS letters

Publication Date

10/1998

Volume

438

Pages

91 - 95

Addresses

Rega Institute for Medical Research, K.U. Leuven, Louvain, Belgium.

Keywords

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