Disease relevance of Benzylacyclouridine

• Because of the clinical toxicities associated with chronic Urd administration, the ability of benzylacyclouridine (BAU) to effect, in vivo, AZT-induced anemia and leukopenia was assessed [1].
• In breast cancer specimens and head-neck squamous carcinomas, however, uridine cleavage was only partially inhibited (40-60%) by 10 or 100 microM BAU [2].
• Therefore, using a tumor-bearing murine model we investigated as to whether low doses of oral Urd coupled with a Urd phosphorylase inhibitor benzylacyclouridine (BAU), would effect safe rescue of FUra toxicity with preservation of antitumor activity [3].

High impact information on Benzylacyclouridine

• The BAU-insensitive phosphorolytic activity in selected tumors, coupled with the potent inhibitory activity of BAU against the "classical" uridine phosphorylase in normal human tissues, provides the rationale for combining BAU with 5-fluorouracil in the treatment of breast and head-neck tumors [2].
• The BAU-insensitive activity requires phosphate and pH conditions similar to the normal enzyme, and the new phosphorolytic activity was independent from thymidine phosphorylase [2].
• Affinity chromatography was utilized to purify UPase from colon 26 and NIH 3T3 cells using the uridine phosphorylase inhibitor 5'-amino benzylacyclouridine linked to an agarose matrix [4].
• The pharmacokinetics, tissue distribution and urinary excretion of the uridine (Urd) phosphorylase (EC 2.4.2.3) inhibitor 5-benzylacyclouridine (BAU) were studied in C57BL/6 female mice by reverse-phase HPLC [5].

Biological context of Benzylacyclouridine

• We prepared a series of 5-aryl-substituted analogues of 5-benzylacyclouridine (BAU), a good inhibitor of UrdPase (IC50 of 0.46 microM), to develop a compound with enhanced potency and improved pharmacokinetics [6].

Associations of Benzylacyclouridine with other chemical compounds

• Potentiation of 5-fluoro-2'-deoxyuridine antineoplastic activity by the uridine phosphorylase inhibitors benzylacyclouridine and benzyloxybenzylacyclouridine [7].
• The modulation of UPase activity by its specific inhibitors such as benzylacyclouridine or the disruption of this gene greatly affects uridine metabolism and pyrimidine nucleotide biosynthesis [8].

References