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Literature summary for 2.2.1.1 extracted from

  • Le Huerou, Y.; Gunawardana, I.; Thomas, A.A.; Boyd, S.A.; de Meese, J.; Dewolf, W.; Gonzales, S.S.; Han, M.; Hayter, L.; Kaplan, T.; Lemieux, C.; Lee, P.; Pheneger, J.; Poch, G.; Romoff, T.T.; Sullivan, F.; Weiler, S.; Wright, S.K.; Lin, J.
    Prodrug thiamine analogs as inhibitors of the enzyme transketolase (2008), Bioorg. Med. Chem. Lett., 18, 505-508.
    View publication on PubMed

Application

Application Comment Organism
drug development ring-opened analogs of the transketolase inhibitor 'N30-pyridyl thiamine'; 3-(6-methyl-2-amino-pyridin-3-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-thiazol-3-ium chloride hydrochloride are effectively transformed in vivo to the active thiazoliums, whereby the effectiveness of this transformation is dependent on the sulfur moiety. The pharmacokinetic properties of the transketolase inhibitor are improved, the Cmax is reduced, thus avoiding toxicity, and higher distribution and exposure correlate in vivo with a stronger and longer inhibition of blood transketolase Mus musculus

Inhibitors

Inhibitors Comment Organism Structure
3-(6-methyl-2-amino-pyridin-3-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-thiazol-3-ium chloride hydrochloride analog of thiamine, potent transketolase inhibitor but suffers from poor pharmacokinetics due to high clearance and Cmax linked toxicity. Efficient way of improving the pharmacokinetic profile is to prepare oxidized prodrugs which are slowly reduced in vivo yielding longer, sustained blood levels of the drug Mus musculus

Organism

Organism UniProt Comment Textmining
Mus musculus P40142 Balb-c mice
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Mus musculus Balb-c P40142 Balb-c mice
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Source Tissue

Source Tissue Comment Organism Textmining
blood
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Mus musculus
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Cofactor

Cofactor Comment Organism Structure
thiamine diphosphate
-
Mus musculus