Synthesis, in vitro and in vivo activity of thiamine antagonist transketolase inhibitors

…, Y Le Huerou, J De Meese, I Gunawardana…

Index: Thomas, Allen A.; Le Huerou; De Meese; Gunawardana, Indrani; Kaplan, Tomas; Romoff, Todd T.; Gonzales, Stephen S.; Condroski, Kevin; Boyd, Steven A.; Ballard, Josh; Bernat, Bryan; DeWolf, Walter; Han, May; Lee, Patrice; Lemieux, Christine; Pedersen, Robin; Pheneger, Jed; Poch, Greg; Smith, Darin; Sullivan, Francis; Weiler, Solly; Wright, S. Kirk; Lin, Jie; Brandhuber, Barb; Vigers, Guy Bioorganic and Medicinal Chemistry Letters, 2008 , vol. 18, # 6 p. 2206 - 2210

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Citation Number: 43

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 ...