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Article

In Silico Prediction of Cytochrome P450-Drug Interaction: QSARs for CYP3A4 and CYP2C9

Department of Earth and Environmental Sciences, University of Milano-Bicocca, P.za della Scienza 1, 20126 Milano, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to the work.
Academic Editor: Jesus Vicente De Julián Ortiz
Int. J. Mol. Sci. 2016, 17(6), 914; https://doi.org/10.3390/ijms17060914
Received: 16 May 2016 / Revised: 1 June 2016 / Accepted: 6 June 2016 / Published: 9 June 2016
Cytochromes P450 (CYP) are the main actors in the oxidation of xenobiotics and play a crucial role in drug safety, persistence, bioactivation, and drug-drug/food-drug interaction. This work aims to develop Quantitative Structure-Activity Relationship (QSAR) models to predict the drug interaction with two of the most important CYP isoforms, namely 2C9 and 3A4. The presented models are calibrated on 9122 drug-like compounds, using three different modelling approaches and two types of molecular description (classical molecular descriptors and binary fingerprints). For each isoform, three classification models are presented, based on a different approach and with different advantages: (1) a very simple and interpretable classification tree; (2) a local (k-Nearest Neighbor) model based classical descriptors and; (3) a model based on a recently proposed local classifier (N-Nearest Neighbor) on binary fingerprints. The salient features of the work are (1) the thorough model validation and the applicability domain assessment; (2) the descriptor interpretation, which highlighted the crucial aspects of P450-drug interaction; and (3) the consensus aggregation of models, which largely increased the prediction accuracy. View Full-Text
Keywords: cytochrome P450; QSAR; CYP2C9; CYP3A4; in silico; ADMET cytochrome P450; QSAR; CYP2C9; CYP3A4; in silico; ADMET
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MDPI and ACS Style

Nembri, S.; Grisoni, F.; Consonni, V.; Todeschini, R. In Silico Prediction of Cytochrome P450-Drug Interaction: QSARs for CYP3A4 and CYP2C9. Int. J. Mol. Sci. 2016, 17, 914. https://doi.org/10.3390/ijms17060914

AMA Style

Nembri S, Grisoni F, Consonni V, Todeschini R. In Silico Prediction of Cytochrome P450-Drug Interaction: QSARs for CYP3A4 and CYP2C9. International Journal of Molecular Sciences. 2016; 17(6):914. https://doi.org/10.3390/ijms17060914

Chicago/Turabian Style

Nembri, Serena, Francesca Grisoni, Viviana Consonni, and Roberto Todeschini. 2016. "In Silico Prediction of Cytochrome P450-Drug Interaction: QSARs for CYP3A4 and CYP2C9" International Journal of Molecular Sciences 17, no. 6: 914. https://doi.org/10.3390/ijms17060914

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