Jean, Pascale published the artcileOxidation of tienilic acid by human yeast-expressed cytochromes P-450 2C8, 2C9, 2C18, and 2C19. Evidence that this drug is a mechanism-based inhibitor specific for cytochrome P-450 2C9, Application In Synthesis of 40180-04-9, the main research area is tienilic acid metabolism liver microsome; cytochrome P450 tienilic acid metabolism.
Oxidation of tienilic acid by human cytochromes P 450 (CYP) 2C9, 2C18, 2C8, and 2C19 was studied using recombinant enzymes expressed in yeast. CYP 2C9 was the best catalyst for 5-hydroxylation of tienilic acid (Km = 5 μM, kcat = 1.7 min ‘), 30-fold more potent in terms of kcat/Km than CYP 2C18 (Km = 150 μM, kcat = 1.8 min ‘) and 300-fold more potent than CYP 2C8 (Km = 145 μM, kcat = 0.2 min-1). CYP 2C19 was unable to catalyze this hydroxylation under our exptl. conditions. A marked effect of the ionic strength on the activities (hydroxylations of tienilic acid and tolbutamide) of these cytochromes P 450 expressed in the yeast strain 334 was observed The effect was particularly great in the case of CYP 2C18, with a tenfold decrease of activity upon increasing ionic strength from 0.02 to 0.1. 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. Tienilic acid thus appears to be a mechanism-based inhibitor specific for CYP 2C9 in human liver. Experiments performed with human liver microsomes confirmed that tienilic acid 5-hydroxylase underwent a time-dependent inactivation during 5-hydroxylation of tienilic acid.
European Journal of Biochemistry published new progress about Enzyme kinetics. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Application In Synthesis of 40180-04-9.
Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem