Biological activity of the potent uridine phosphorylase inhibitor 5-ethyl-2,2'-anhydrouridine
Veres, Z.; Szinai, I.; Szabolcs, A.; Ujszászy, K.; Dénes, G.
Drugs under Experimental and Clinical Research 13(10): 615-621
1987
ISSN/ISBN: 0378-6501 PMID: 3428126 Document Number: 301141
5-Ethyl-2,2'-anhydrouridine (ANEUR) proved to be a potent inhibitor of uridine phosphorylase isolated from sarcoma 180 cells with an apparent Ki (Ki(app) value of 99 nM. Coadministration of ANEUR with 5-fluorouridine (FUR) resulted in increased toxicity of FUR. The LD50 value of FUR alone was 9 mg/kg (when administered for 5 consecutive days) while the LD50 was 3 mg/kg when FUR was administered together with ANEUR in vivo. There was no significant difference in mean tumor weight on day 10 between control animals and animals treated with FUR (5 mg/kg/day for 3 days) or ANEUR (280 mg/kg/day for 3 days). When FUR was coadministered with ANEUR, mean tumor weight was 91% less than that of the untreated controls, showing that ANEUR, the potent URPase inhibitor, increases the antitumor effect of FUR.