TY - JOUR T1 - An <em>in Vivo</em> and <em>in Vitro</em> Evaluation of 1-β-D-Ribofuranosyl-1,2,4-triazole-3-carboxamidine: An Inhibitor of Human Lymphoblast Purine Nucleoside Phosphorylase JF - Molecular Pharmacology JO - Mol Pharmacol SP - 287 LP - 295 VL - 18 IS - 2 AU - RANDALL C. WILLIS AU - ROLAND K. ROBINS AU - J. EDWIN SEEGMILLER Y1 - 1980/09/01 UR - http://molpharm.aspetjournals.org/content/18/2/287.abstract N2 - The synthetic nucleoside analog, 1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine (TCNR), is a competitive, reversible inhibitor of inosine phosphorolysis by human lymphoblast punne nucleoside phosphorylase. TCNR is not a substrate for the enzyme. The apparent Ki of TCNR is 5 x 10-6 M under conditions providing an apparent Km of 2.5 x 10-5 M for inosine phosphorolysis. In both in vivo and in vitro assays TCNR is 7-10 times more potent than a previously described inhibitor of purine nucleoside phosphorylase, Formycin B. TCNR and Formycin B have growth inhibitory properties unrelated to inhibition of purine nucleoside phosphorylase. This additional effect of TCNR, inhibition of IMP dehydrogenase, is eliminated in studies using lymphoblast lines deficient in adenosine kinase, but this mutation has no effect on the growth inhibition produced by Formycin B. The primary effect of TCNR on purine nucleoside phosphorylase in intact cells is best demonstrated with a human lymphoblast line deficient in both adenosine kinase and hypoxanthine-guanine phosphoribosyltransferase which allows accumulation of inosine, guanosine, deoxyinosine, and deoxyguanosine in the medium. The accumulation of these nucleosides does not inhibit the growth of the human B lymphoblast. ER -