Drug-oxidizing and conjugating non-cytochrome P450 (non-P450) enzymes in cynomolgus monkeys and common marmosets as preclinical models for humans

Biochem Pharmacol. 2021 Dec 27:114887. doi: 10.1016/j.bcp.2021.114887. Online ahead of print.ABSTRACTMany drug oxidations and conjugations are mediated by a variety of cytochromes P450 (P450) and non-P450 enzymes in humans and non-human primates. These non-P450 enzymes include aldehyde oxidases (AOX), carboxylesterases (CES), flavin-containing monooxygenases (FMO), glutathione S-transferases (GST), arylamine N-acetyltransferases (NAT),sulfotransferases (SULT), and uridine 5'-diphospho-glucuronosyltransferases (UGT) and their substrates include both endobiotics and xenobiotics. Cynomolgus macaques (Macaca fascicularis, an Old-World monkey) are widely used in preclinical studies because of their genetic and physiological similarities to humans. However, many reports have indicated the usefulness of common marmosets (Callithrix jacchus, a New World monkey) as an alternative non-human primate model. Although knowledge of the drug-metabolizing properties of non-P450 enzymes in non-human primates is relatively limited, new research has started to provide an insight into the molecular characteristics of these enzymes in cynomolgus macaques and common marmosets. This mini-review provides collective information on the isoforms of non-P450 enzymes AOX, CES, FMO, GST, NAT, SULT, and UGT and their enzymatic profiles in cynomolgus macaques and common marmosets. In general, these non-P450 cynomolgus macaque and marmoset enzymes have high sequence identities and similar substrate recognitio...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Source Type: research