Exploring the Chemical Space of P-Glycoprotein Interacting Compounds

Mini Reviews in Medicinal Chemistry
Veda PrachayasittikulChanin Nantasenamat

Abstract

P-glycoprotein (Pgp) is well known for its clinical importance in the pharmacokinetics of drugs and its role in multidrug resistance. The promiscuity of Pgp that arises from its ability to extrude a wide range of lipophilic and structurally unrelated compounds from cells, render the classification and understanding of its interacting compounds a great challenge. In this study, a data set of Pgp-interacting compounds including 1463 inhibitors, 1085 noninhibitors, 308 substrates and 126 non-substrates was retrieved and subjected to a combination of analyses, including exploration of chemical space, statistical analysis of descriptor values and molecular fragment analysis, to obtain insight into distinct physicochemical properties and important chemical substructures which may govern the biological activity of investigated compounds toward Pgp. Statistical analysis of descriptor values and molecular fragment analysis indicated that particular size, shape, functional groups and molecular fragments may govern the classification of Pgp-interacting compounds by influencing their physicochemical properties and their interaction with Pgp. Overall, the interacting compounds (i.e., substrates and inhibitors) are larger in size, more flexi...Continue Reading

Citations

Jan 7, 2017·SAR and QSAR in Environmental Research·V PrachayasittikulC Nantasenamat
May 21, 2019·Expert Opinion on Drug Delivery·Behzad JafariYadollah Omidi
Jul 25, 2021·International Journal of Molecular Sciences·Małgorzata FabijańskaJustyn Ochocki

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