Non-CYP Mediated MetabolismIn vitro Metabolism
• Metabolic stability and metabolite identification
• Identification of metabolising enzymes
• Recombinant FMO, MAO, CE, AOX, UGT, SULT, NAT
• Liver microsomes, S9, cytosol, and hepatocytes or extrahepatic tissues
If CYP-focused metabolic enzyme identification 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 a flavin containing mono-oxygenases (FMO), monoamine-oxidases (MAO), carboxylesterases (CE), aldehyde oxidase (AOX), UDP glucuronosyltransferases (UGT), sulfotransferases (SULT) or N-acetyltransferases (NAT). Approaches using liver microsomes, S9, cytosol, or hepatocytes with enzyme-selective inhibitors are also sometimes used.