Studies to further investigate the inhibition of human liver microsomal CYP2C8 by the acyl-β-glucuronide of gemfibrozil was written by Jenkins, S. M.;Zvyaga, T.;Johnson, S. R.;Hurley, J.;Wagner, A.;Burrell, R.;Turley, W.;Leet, J. E.;Philip, T.;Rodrigues, A. D.. And the article was included in Drug Metabolism and Disposition in 2011.Recommanded Product: 59960-32-6 This article mentions the following:
In previous studies, gemfibrozil acyl-β-glucuronide, but not gemfibrozil, was found to be a mechanism-based inhibitor of cytochrome P 450 2C8. To better understand whether this inhibition is specific for gemfibrozil acyl-β-glucuronide or whether other glucuronide conjugates are potential substrates for inhibition of this enzyme, we evaluated several pharmaceutical compounds (as their acyl glucuronides) as direct-acting and metabolism-dependent inhibitors of CYP2C8 in human liver microsomes. Of 11 compounds that were evaluated as their acyl glucuronide conjugates, only gemfibrozil acyl-β-glucuronide exhibited mechanism-based inhibition, indicating that CYP2C8 mechanism-based inhibition is very specific to certain glucuronide conjugates. Structural analogs of gemfibrozil were synthesized, and their glucuronide conjugates were prepared to further examine the mechanism of inhibition. When the aromatic Me groups on the gemfibrozil moiety were substituted with trifluoromethyls, the resulting glucuronide conjugate was a weaker inhibitor of CYP2C8 and mechanism-based inhibition was abolished. However, the glucuronide conjugates of monomethyl gemfibrozil analogs were mechanism-based inhibitors of CYP2C8, although not as potent as gemfibrozil acyl-β-glucuronide itself. The ortho-monomethyl analog was a more potent inhibitor than the meta-monomethyl analog, indicating that CYP2C8 favors the ortho position for oxidation and potential inhibition. Mol. modeling of gemfibrozil acyl-β-glucuronide in the CYP2C8 active site is consistent with the ortho-Me position being the favored site of covalent attachment to the heme. Moreover, hydrogen bonding to four residues (Ser100, Ser103, Gln214, and Asn217) is implicated. In the experiment, the researchers used many compounds, for example, 2-(3-(Hydroxy(phenyl)methyl)phenyl)propanoic acid (cas: 59960-32-6Recommanded Product: 59960-32-6).
2-(3-(Hydroxy(phenyl)methyl)phenyl)propanoic acid (cas: 59960-32-6) belongs to alcohols. Alcohols are weak acids. The most acidic simple alcohols (methanol and ethanol) are about as acidic as water, and most other alcohols are somewhat less acidic. The most common reactions of alcohols can be classified as oxidation, dehydration, substitution, esterification, and reactions of alkoxides.Recommanded Product: 59960-32-6
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts