Human metabolism of AM6-36, a retinoid X receptor-alpha ligand

摘要

Six metabolites of the RXR(alpha) ligand AM6-36 were produced in vitro using human liver microsomes and human liver hepatocytes. The in vitro metabolites of AM6-36 were identified by comparison with synthetic standards using high resolution accurate mass measurements, product ion tandem mass spectrometry, and co-injection during LC-MS-MS. The metabolism pathways included N-acetylation, ketone reduction to an alcohol, and conversion of primary amino groups into alcohols. Based on the affinity binding studies using ultrafiltation LC-MS, none of the metabolites of AM6-36 were found to be ligands of RXR(alpha). In vivo studies of metabolism and cancer chemoprevention are planned for AM6-36.