Recent Advances on P-Glycoprotein (ABCB1) Transporter Modelling with In Silico Methods

ABC transporters play a critical role in both drug bioavailability and toxicity, and with the discovery of the P-glycoprotein (P-gp), this became even more evident, as it plays an important role in preventing intracellular accumulation of toxic compounds. Over the past 30 years, intensive studies have been conducted to find new therapeutic molecules to reverse the phenomenon of multidrug resistance (MDR) ), that research has found is often associated with overexpression of P-gp, the most extensively studied drug efflux transporter; in MDR, therapeutic drugs are prevented from reaching their targets due to active efflux from the cell. The development of P-gp inhibitors is recognized as a good way to reverse this type of MDR, which has been the subject of extensive studies over the past few decades. Despite the progress made, no effective P-gp inhibitors to reverse multidrug resistance are yet on the market, mainly because of their toxic effects. Computational studies can accelerate this process, and in silico models such as QSAR models that predict the activity of compounds associated with P-gp (or analogous transporters) are of great value in the early stages of drug development, along with molecular modelling methods, which provide a way to explain how these molecules interact with the ABC transporter. This review highlights recent advances in computational P-gp research, spanning the last five years to 2022. Particular attention is given to the use of machine-learning approaches, drug–transporter interactions, and recent discoveries of potential P-gp inhibitors that could act as modulators of multidrug resistance.