Subject Area物理化学
Pattern-recognition-based Prediction of Metabolic Regioselectivity Mediated by Human Cytochromes P450 3A4
Ai CZ(艾纯芝); Mao YX(毛玉玺); Yang L(杨凌)
Conference Name9th International Meeting of the International-Society-for-the-Study-of-Xenobiotics(ISSX)
Conference Date2010-09-04
Conference Place土耳其
Funding Organization国际药代学会
AbstractP450 3A4, the most important human CYP enzyme, is responsible for the metabolism of more than 50%-60% of clinically used drugs. Early knowing the site of metabolism will help the medicinal chemist to decide how best to block the metabolism of candidates in drug discovery. Traditionally, the regioselectivity has always been evaluated by estimating the dehydrogenation energy, and/or the binding poses of substrates in the active site of the enzyme. Here, we present a novel strategy for predicting the metabolic regioselectivity mediated by human cytochrome P450 3A4. We have defined a novel type of fragmental-based descriptors that was used together with the E-state molecular descriptors to establish the model for predicting the site of metabolism. With pattern recognition method, 127 substrates of P450 3A4 collected from literatures were employed to develop the model. The cross-validated prediction result is 79% and the accuracy for predicting one right site is higher than 88%, suggesting the efficiency of the newly defined fragmental-based descriptors. The predictability of this model is as good as the recently published QSAR model proposed by Sheridan et al1. 1. Sheridan, R. P.; Korzekwa, K. R.; Torres, R. A.; Walker, M. J., Empirical regioselectivity models for human cytochromes p450 3A4, 2D6, and 2C9. Journal of Medicinal Chemistry 2007, 50, (14), 3173-3184.
WOS IDWOS:000281147700335
Citation statistics
Document Type会议论文
Corresponding AuthorYang L(杨凌)
Recommended Citation
GB/T 7714
Ai CZ,Mao YX,Yang L. Pattern-recognition-based Prediction of Metabolic Regioselectivity Mediated by Human Cytochromes P450 3A4[C],2010:188/2.
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