Lecoeur, Sylvaine published the artcileSpecificity of in vitro Covalent Binding of Tienilic Acid Metabolites to Human Liver Microsomes in Relationship to the Type of Hepatotoxicity: Comparison with Two Directly Hepatotoxic Drugs, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is tienilate metabolite binding liver microsome hepatotoxicity; cytochrome P4502C9 tienilate binding antibody formation.
To better understand the first steps leading to drug-induced immunoallergic hepatitis, the authors studied the target of anti-LKM2 autoantibodies appearing in tienilic acid-induced hepatitis, and the target of tienilic acid-reactive metabolites. It was identified as cytochrome P 450 2C9, (P 450 2C9): indeed,anti-LKM2 specifically recognized P 450 2C9, but none of the other P450s tested (including other 2C subfamily members, 2C8 and 2C18). Tienilic acid-reactive metabolite(s) specifically bound to P 4502C9, and experiments with yeast expressing active isolated P450s showed that P 450 2C9 was responsible for tienilic acid-reactive metabolite(s) production Results of qual. and quant. covalent binding of tienilic acid metabolite(s) to human liver microsomes were then compared to those obtained with two drugs leading to direct toxic hepatitis, namely, acetaminophen and chloroform. Kinetic constants (Km and Vmax) were measured, and the covalent binding profile of the metabolites to human liver microsomal proteins was studied. Tienilic acid had both the lowest Km and the highest covalent binding rate at pharmacol. doses. For acetaminophen and chloroform, several microsomal proteins were covalently bound, while covalent binding was highly specific for tienilic acid and dihydralazine, another drug leading to immunoallergic hepatitis. Although low numbers of drugs were tested, these results led the authors to think that there may exist a relation between the specificity of covalent binding and the type of hepatotoxicity.
Chemical Research in Toxicology published new progress about Autoantibodies, monoclonal Role: BIOL (Biological Study). 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, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.
Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem