Background: Non-human primates are valuable animal models in drug discovery and biomedical research.
Human CYP2D6 accounts for 1.3-4.3% of total hepatic CYP content in the liver, but is involved in the metabolism
of more than 150 drugs. With the advancement of genomic sequencing and annotation, a panel of CYP2D
genes have been cloned from non-human primates. This review highlights the similarities and differences of these
CYP2D genes non-human primates.
Methods: We conducted a structured PubMed search using a focused review question and proper inclusion/exclusion criteria. The quality
of retrieved papers was assessed and briefed using standard tools and expert knowledge.
Results: Most studies on CYP expression in non-human primates have been carried out in the cynomolgus and Rhesus monkeys. Deduced
amino acid sequences of primate CYP2D cDNAs share high sequence identity (93-96%) with human CYP2D6. The chimpanzee
genome has CYP2D6 and 2D7 but bonobos only contain CYP2D6. The CYP2D6 gene is located on chromosome 22 in the chimpanzee
genome (human CYP2D6 maps to chromosome 22q13.1), and on chromosome 10 in the genome of the Rhesus monkey. Cynomolgus
monkey CYP2D17 and Japanese monkey 2D29 metabolize bufuralol and dextromethorphan. CYP2D17 metabolizes bufuralol and dextromethorphan,
whereas CYP2D29 metabolizes bufuralol and debrisoquine. In addition, quinidine inhibits both cynomolgus monkey
CYP2D17 and Japanese monkey 2D29.
Conclusion: The CYP2D members from non-human primates show differential genomic contexts, catalytic activities toward substrates
and inhibitory profiles. Further studies are warranted to elucidate the structural and functional features of CYP2D members in non-human
primates and thus offer a solid base for the application of these animals in drug discovery.