7-Deazaxanthine, a novel prototype inhibitor of thymidine phosphorylase.
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.
Balzarini
J
J
Rega Institute for Medical Research, K.U. Leuven, Louvain, Belgium.
Gamboa
A E
AE
Esnouf
R
R
Liekens
S
S
Neyts
J
J
De Clercq
E
E
Camarasa
M J
MJ
Pérez-Pérez
M J
MJ
D000482:Allantois / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001665:Binding Sites; D001976:Bromouracil / Q000031:analogs & derivatives / Q000494:pharmacology; D002642:Chick Embryo; D002823:Chorion / Q000187:drug effects / Q000502:physiology; D003510:Cyclohexanes; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors*; D013941:Thymine / Q000378:metabolism; D014970:Xanthines / Q000737:chemistry / Q000494:pharmacology*
C115661:7-deazaxanthine; D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D004791:Enzyme Inhibitors; D012717:Sesquiterpenes; D014970:Xanthines; D001976:Bromouracil; C039893:6-amino-5-bromouracil; D013939:Thymidine Phosphorylase; D013941:Thymine; D013936:Thymidine; D000077609:O-(Chloroacetylcarbamoyl)fumagillol