| Autor: |
Thomas AA; Array BioPharma Inc., 3200 Walnut Street, Boulder, CO 80301, USA. athomas@arraybiopharma.com, Le Huerou Y, De Meese J, Gunawardana I, Kaplan T, Romoff TT, Gonzales SS, Condroski K, Boyd SA, Ballard J, Bernat B, DeWolf W, Han M, Lee P, Lemieux C, Pedersen R, Pheneger J, Poch G, Smith D, Sullivan F, Weiler S, Wright SK, Lin J, Brandhuber B, Vigers G |
| Jazyk: |
angličtina |
| Zdroj: |
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2008 Mar 15; Vol. 18 (6), pp. 2206-10. Date of Electronic Publication: 2007 Dec 03. |
| DOI: |
10.1016/j.bmcl.2007.11.101 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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