Artificial intelligence to predict inhibitors of drug-metabolizing enzymes and transporters for safer drug design

Introduction: Drug-metabolizing enzymes (DMEs) and transporters (DTs) play integral roles in drug metabolism and drug–drug interactions (DDIs) which directly impact drug efficacy and safety. It is well-established that inhibition of DMEs and DTs often leads to adverse drug reactions (ADRs) and therapeutic failure. As such, early prediction of such inhibitors is vital in drug development. In this context, the limitations of the traditional in vitro assays and QSAR models methods have been addressed by harnessing artificial intelligence (AI) techniques. Areas covered: This narrative review presents the insights gained from the application of AI for predicting DME and DT inhibitors over the past decade. Several case studies demonstrate successful AI applications in enzyme-transporter interaction prediction, and the authors discuss workflows for integrating these predictions into drug design and regulatory frameworks. Expert opinion: The application of AI in predicting DME and DT inhibitors has demonstrated significant potential toward enhancing drug safety and effectiveness. However, critical challenges involve the data quality, biases, and model transparency. The availability of diverse, high-quality datasets alongside the integration of pharmacokinetic and genomic data are essential. Lastly, the collaboration among computational scientists, pharmacologists, and regulatory bodies is pyramidal in tailoring AI tools for personalized medicine and safer drug development.