Tienilic Acid |
| Catalog No.GC12211 |
specific suicide substrate for CYP2C9 and CYP2C10
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 40180-04-9
Sample solution is provided at 25 µL, 10mM.
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Km: 5 microM for CYP 2C9 catalyzing 5-hydroxylation of tienilic acid
Tienilic acid is a specific suicide substrate for CYP2C9 and CYP2C10.
Cytochrome P450 enzymes function to metabolize both endogenous and exogenous xenobiotics. Both the 3A and 2C isoforms are present in human liver of which CYP2C9 appears most highly expressed.
In vitro: Oxidation of tienilic acid by human CYP 2C9, 2C18, 2C8 and 2C19 was studied. Results showed that CYP 2C9 was the best catalyst for 5-hydroxylation of tienilic acid, 30-fold more potent in terms of kcat/K(m) than CYP 2C18 and 300-fold more potent than CYP 2C8. CYP 2C19 was unable to catalyze this hydroxylation under our experimental conditions. Specific-covalent binding of tienilic acid metabolites to cytochrome P-450 was markedly higher upon tienilic acid oxidation by CYP 2C9 than by CYP 2C18 and CYP 2C8. Mechanism-based inactivation of cytochrome P-450 during tienilic acid oxidation was observed in the case of CYP 2C9 but was not detectable with CYP 2C18 and CYP 2C8. Therefore, tienilic acid appeared to be a mechanism-based inhibitor specific for CYP 2C9 in human liver [1].
In vivo: Animal study found that the short-term treatment of tienilic acid for 2 weeks at 450 mg per kg per day could increase the activity of microsomal epoxide hydrolase in both rat liver and kidneys. Moreover, the effect of tienilic acid on the activity of microsomal epoxide hydrolase in the rat liver correlated with the dose at levels of 20-450 mg per kg per day for 14 days. In addition, tienilic acid had only marginal effects on cytochrome-P-450-mediated mono-oxygenases [2].
Clinical trial: So far, no clinical study has been conducted.
References:
[1] Jean, P. ,Lopez-Garcia, P.,Dansette, P.M., et al. Oxidation of tienilic acid by human yeast-expressed cytochromes P450 2C8, 2C9, 2C18 and 2C19: Evidence that this drug is a mechanism-based inhibitor specific of cytochrome P450 2C9. European Journal of Biochemistry 241, 797-804 (1996).
[2] Sellman R, Parkki MG. Induction of microsomal epoxide hydrolase by tienilic acid in the rat. J Appl Toxicol. 1983 Oct;3(5):245-8.
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