| Literature DB >> 18267359 |
Allen A Thomas1, Y Le Huerou, J De Meese, Indrani Gunawardana, Tomas Kaplan, Todd T Romoff, Stephen S Gonzales, Kevin Condroski, Steven A Boyd, Josh Ballard, Bryan Bernat, Walter DeWolf, May Han, Patrice Lee, Christine Lemieux, Robin Pedersen, Jed Pheneger, Greg Poch, Darin Smith, Francis Sullivan, Solly Weiler, S Kirk Wright, Jie Lin, Barb Brandhuber, Guy Vigers.
Abstract
Tumor cells extensively utilize the pentose phosphate pathway for the synthesis of ribose. Transketolase is a key enzyme in this pathway and has been suggested as a target for inhibition in the treatment of cancer. In a pharmacodynamic study, nude mice with xenografted HCT-116 tumors were dosed with 1 ('N3'-pyridyl thiamine'; 3-(6-methyl-2-amino-pyridin-3-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-thiazol-3-ium chloride hydrochloride), an analog of thiamine, the co-factor of transketolase. Transketolase activity was almost completely suppressed in blood, spleen, and tumor cells, but there was little effect on the activity of the other thiamine-utilizing enzymes alpha-ketoglutarate dehydrogenase or glucose-6-phosphate dehydrogenase. Synthesis and SAR of transketolase inhibitors is described.Entities:
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Year: 2007 PMID： 18267359 DOI： 10.1016/j.bmcl.2007.11.101
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823