The role of carbonyl reductase 1 in drug discovery and development.

INTRODUCTION: Carbonyl reductase 1 (CBR1) plays a critical role in drug metabolism of ketones and aldehydes. CBR1 has broad substrate specificity and is involved in metabolizing a number of clinically important drugs. Areas covered: The impact of CBR1 in drug metabolism and disposition are discussed. The CBR1 enzyme is covered in detail including discussion on topics such as tissue distribution, species difference, individual variability, the effect of genetic polymorphism and disease state, iGnducibility and drug-drug interaction potential. The structure and function of CBR1 and CBR3 are also compared. In addition, the formation of chiral alcohols from CBR1 reduction and MIST coverage are reviewed. Expert Opinion: As CBR1 is an emerging enzyme in drug discovery and development, much research is needed to further understand its role in drug metabolism and disposition. In vitro-in vivo correlation for CBR1-mediated clearance is mostly unknown. Selective CBR1 inhibitors and substrates are not well enough characterized for reaction phenotyping of the CBR1 pathway. Multiple pathways appear to be involved in the regulation of CBR1. Future investigation will also help reveal their impact on drug-drug interaction potentials and the influence of individual variability.