Survey of Machine Learning Techniques for Prediction of the Isoform Specificity of Cytochrome P450 Substrates

Background: Determination or prediction of the Absorption, Distribution, Metabolism, and Excretion (ADME) properties of drug candidates and drug-induced toxicity plays crucial roles in drug discovery and development. Metabolism is one of the most complicated pharmacokinetic properties to be understood and predicted. However, experimental determination of the substrate binding, selectivity, sites and rates of metabolism is time- and recourse- consuming. In the phase I metabolism of foreign compounds (i.e., most of drugs), cytochrome P450 enzymes play a key role. To help develop drugs with proper ADME properties, computational models are highly desired to predict the ADME properties of drug candidates, particularly for drugs binding to cytochrome P450. Objective: This narrative review aims to briefly summarize machine learning techniques used in the prediction of the cytochrome P450 isoform specificity of drug candidates. Results: Both single-label and multi-label classification methods have demonstrated good performance on modelling and prediction of the isoform specificity of substrates based on their quantitative descriptors. Conclusion: This review provides a guide for researchers to develop machine learning-based methods to predict the cytochrome P450 isoform specificity of drug candidates.