Prodrug thiamine analogs as inhibitors of the enzyme transketolase.

  title={Prodrug thiamine analogs as inhibitors of the enzyme transketolase.},
  author={Yvan Le Hu{\'e}rou and Indrani W Gunawardana and Allen A Thomas and Steven A Boyd and Jason de Meese and Walter E. deWolf and Steven S Gonzales and May Sabai Han and Laura Hayter and Tomas Kaplan and Christine Lemieux and Patrice A Lee and Jed A Pheneger and Gregory Poch and Todd T Romoff and Francis Sullivan and Solly Weiler and S Kirk Wright and Jie Min Lin},
  journal={Bioorganic & medicinal chemistry letters},
  volume={18 2},
Transketolase, a key enzyme in the pentose phosphate pathway, has been suggested as a target for inhibition in the treatment of cancer. Compound 5a ('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 the transketolase cofactor thiamine, is a potent transketolase inhibitor but suffers from poor pharmacokinetics due to high clearance and C(max) linked toxicity. An efficient way of improving the… CONTINUE READING


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