Benzylacyclouridine (BAU) 是一种有效且特异性的尿苷磷酸化酶抑制剂，尿苷磷酸化酶是尿苷分解代谢中的第一种酶。Benzylacyclouridine 可以调节 5-氟尿嘧啶 (5-FU) 及其衍生物的细胞毒副作用。
Benzylacyclouridine (BAU) is a potent and specific inhibitor of uridine phosphorylase, the first enzyme in the catabolism of uridine. Benzylacyclouridine can modulate the cytotoxic side effects of 5-fluorouracil (5-FU) and its derivatives[1][2][3].
Benzylacyclouridine increases 5-FU-induced cytotoxicity in a number of human cancer cell lines[1].Benzylacyclouridine (20-100 μM) reduces the rapid clearance of trace amounts of either [14C]uridine or hyperphysiologic concentrations of non-labeled uridine by the isolated rat liver perfused with an artificial oxygen carrier[2].
Benzylacyclouridine (p.o. or i.v.) arrests the rapid degradation of a tracer dose of uridine into uracil in dogs and pigs[1].Benzylacyclouridine exhibits the t1/2 of 1.8-3.6 h in dogs, with bioavailability levels of 85% (30 mg/kg) and 42.5% (120 mg/kg)[1].Benzylacyclouridine (120 mg/kg) exhibits the t1/2 of 1.6-2.3 h, with a bioavailability of 40% in pigs[1].
[1]. Pizzorno G, et, al. Phase I clinical and pharmacological studies of benzylacyclouridine, a uridine phosphorylase inhibitor. Clin Cancer Res. 1998 May;4(5):1165-75.
[2]. Monks A, et, al. Effect of 5-benzylacyclouridine, a potent inhibitor of uridine phosphorylase, on the metabolism of circulating uridine by the isolated rat liver. Biochem Pharmacol. 1983 Jul 1;32(13):2003-9.
[3]. Roosild TP, et, al. Implications of the structure of human uridine phosphorylase 1 on the development of novel inhibitors for improving the therapeutic window of fluoropyrimidine chemotherapy. BMC Struct Biol. 2009 Mar 16;9:14.
动态评分
0.0