Development of in silico Metabolic Stability prediction for Cytochrome P450 3A4

다국어 초록 (Multilingual Abstract)

Metabolic stability is an important property of drug candidates. Most of the drug metabolism occurs by cytochrome P450 isoenzymes and the accurate prediction of CYP450-mediated metabolic reactions is necessary for efficient drug discovery. The EaMEAD method previously described enables early prediction of the regioselectivity of metabolic reactions in a practical and efficient manner. We developed the simulation method of first-order reaction kinetics for the quantitative drug metabolism reaction of CYP450 3A4. The predicted drug metabolic stabilities were compared with the experimental % remaining of drug after 30min. The reliability and ease of use of this model will greatly facilitate early stage PK predictions and rational drug design.