Detail of "35943-35-2"

Reference

Exit transport of a cyclic nucleotide from mouse L-cells

Exit transport of a cyclic nucleotide from mouse L-cells. Plagemann, Peter G. W.; Erbe, John (Med. Sch., Univ. Minnesota, Minneapolis, Minn., USA). J. Biol. Chem., 252(6), 2010-6 (English) 1977. CODEN: JBCHA3. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacodynamics) At a concn. of 30 .mu.M, NSC-154020 (I) [35943-35-2] a tricyclic, 7-deazapurine nucleoside, was rapidly taken up by cultured mouse L cells and converted to intracellular I monophosphate [61966-08-3] but not further metabolized. The I-monophosphate was also excreted by the cells into the medium. It was released by a saturable process against a concn. gradient and the release was inhibited by various inhibitors of energy prodn. This inhibition correlates with a depletion of ATP from the cells. Thus, I-monophosphate excretion probably involves an active transport system. This transport system was highly temp.-dependent (the Q10 falls between 3 and 4) and was inhibited by papaverine, theophylline, Persantin, probenecid, phenethyl alc., and p-chloromercuribenzoate, but not by 500 .mu.M cyclic AMP, AMP, or adenosine. Signficant amts. of various natural phosphorylated intermediates (AMP, ATP, UTP, UMP, UDP-hexoses, and phosphorylcholine) are not released from the cells under similar exptl. conditions either in the absence or presence of 30 .mu.M I.

Metabolism and disposition of 3-amino-1,5-dihydro-5-methyl-1-b-D-ribofuranosyl-1,4,5,6,8-pentaazaac enaphthylene in the rat

Metabolism and disposition of 3-amino-1,5-dihydro-5-methyl-1-b-D-ribofuranosyl-1,4,5,6,8-pentaazaac enaphthylene in the rat. Basseches, Peter J.; Powis, Garth (Dep. Oncol., Mayo Clin., Rochester, MN 55905, USA). Cancer Res., 44(9), 3672-8 (English) 1984. CODEN: CNREA8. ISSN: 0008-5472. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Tricyclic nucleoside NSC 154020 (TCN) [35943-35-2] is a 7-deazapurine nucleoside possessing antitumor activity towards certain tumor cell lines in vitro. In vivo, TCN is readily interconvertible with its 5'-monophosphate ester [61966-08-3]. The present study demonstrates that TCN is metabolized by rat liver microsomes to a ring-opened bicyclic metabolite with loss of cytotoxicity toward Chinese hamster ovary cells in culture. Metab. is mediated by hydrogen peroxide generated by the rat liver microsomes but is not dependent on cytochrome P 450. Isolated hepatocytes prepd. from rat do not form detectable amts. of the ring-opened bicyclic metabolite. Unchanged TCN and the ring-opened bicyclic metabolite are excreted in the bile of rats with a cannulated bile duct, comprising 42 and 12% of an i.v. dose of TCN in 8 h, resp. The ring-opened bicyclic metabolite is not formed by red blood cells in vitro and could not be detected in blood in vivo. The fact that the ring-opened bicyclic metabolite appears in bile suggests that liver cells not present or not active in isolated hepatocyte prepns. might produce the metabolite. Alternatively, the metabolite might be formed directly from TCN in bile, perhaps by hydrogen peroxide excreted into bile. In vivo, 56% of radiolabel was found in the upper and lower gastrointestinal tract and the feces 24 h after an i.p. or i.v. dose of 100 mg of [5-methyl-14C]TCN/sq m. Urinary excretion of radiolabel was 21% of the dose of [14C]TCN in 24 h. Biliary excretion of radiolabel was 65% of the dose of [14C]TCN in 8 h. The fraction of radioactivity undergoing enterohepatic cycling with reabsorption from the gastrointestinal tract after excretion in bile is 84%.