About P-glycoprotein: a new drugable domain is emerging from structural data

P-glycoprotein (P-gp) has been considered an important molecular target in the reversal of multidrug resistance (MDR). As such, the development of P-gp modulators able to restore drug sensitivity in resistant cells is still considered one of the most promising strategies for overcoming MDR. Since the identification of the P-gp's role in MDR, several studies have been performed in order to develop effective P-gp modulators and understand the efflux mechanism. However, no efflux modulator is still clinically available for treating multidrug-resistant cancers. Nevertheless, recent experimental studies suggest that MDR can be surpassed by targeting a specific region within the ABC transporter structure rather than the polyspecific drug-binding pocket. This article will focus on the information available about this new target region and on a brief overview of which scaffolds would be suitable for modulating P-gp at this new location. WIREs Comput Mol Sci 2017, 7:e1316. doi: 10.1002/wcms.1316. For further resources related to this article, please visit the WIREs website.