Title:In silico Strategies to Probe Stereoselective Interactions of Multidrug Resistant Transporter P-glycoprotein
VOLUME: 13 ISSUE: 8
Author(s):Ishrat Jabeen
Affiliation:Research Center for Modeling and Simulations (RCMS), National University of Sciences and Technology (NUST), Sector H-12, 44000, Islamabad, Pakistan.
Keywords:P-glycoprotein, MDR transporter, stereoselectivity, QSAR, pharmacophore, molecular docking.
Abstract:ATP-dependent xenobiotic efflux transporter P-glycoprotein (P-gp) limits the cellular accumulation of many
therapeutically important drug molecules. The most prominent of these are CNS active compounds and the potential chemotherapeutic
agents. Co-administration of chemotherapeutic agents with modulators of P-glycoprotein has been advocated
as a promising concept to circumvent drug resistance in tumor cells. Several pharmacoinformatics strategies to investigate
ligand-P-glycoprotein interactions profiles revealed that these are promiscuous, multi-site and conformational
dependent processes that take place in asymmetric 3D space within the binding cavity of P-gp. Therefore, avoiding stereoselectivity
associated with ligand-protein interaction may compromise efficiency of the QSAR and other modeling strategies.
Within this article, several SAR and QSAR strategies in combination with molecular docking studies on stereoisomeric
inhibitors of P-gp will be highlighted to further explore the stereoselectivity of ligand-P-glycoprotein interaction.
