Non-CYP Mediated MetabolismIn vitro Metabolism
• Metabolic stability and metabolite identification
• Phenotyping of metabolizing enzymes
• UGT, SULT, NAT, FMO, MAO, CE, ALDH, AOX, XO, AKR, CR
• Recombinant enzymes, liver microsomes, S9, cytosol, and hepatocytes or extrahepatic tissues
If CYP-focused enzyme phenotyping assays do not show clear results, non-CYP mediated metabolism should be studied and the enzymes involved in the metabolic processes identified. This can be done by using recombinant enzymes, such as UDP glucuronosyltransferases (UGT), sulfotransferases (SULT), N-acetyltransferases (NAT), flavin containing mono-oxygenases (FMO), monoamine-oxidases (MAO), carboxylesterases (CE), or aldehyde dehydrogenase (ALDH). Metabolism via aldehyde oxidase (AOX), xanthine oxidase (XO), aldo-keto reductase (AKR) and carbobyl reductase (CR) can be investigated by using human liver cytosol with enzyme-selective inhibitors.