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Publication
Structure and ligand-based design of P-glycoprotein inhibitors: a historical perspective
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Advisor(s)
Abstract(s)
Computer-assisted drug design (CADD) is a valuable approach for the discovery of new chemical entities in the field of cancer
therapy. There is a pressing need to design and develop new, selective, and safe drugs for the treatment of multidrug resistance (MDR)
cancer forms, specifically active against P-glycoprotein (P-gp). Recently, a crystallographic structure for mouse P-gp was obtained.
However, for decades the design of new P-gp inhibitors employed mainly ligand-based approaches (SAR, QSAR, 3D-QSAR and phar macophore studies), and structure-based studies used P-gp homology models. However, some of those results are still the pillars used as a
starting point for the design of potential P-gp inhibitors. Here, pharmacophore mapping, (Q)SAR, 3D-QSAR and homology modeling,
for the discovery of P-gp inhibitors are reviewed. The importance of these methods for understanding mechanisms of drug resistance at a
molecular level, and design P-gp inhibitors drug candidates are discussed. The examples mentioned in the review could provide insights
into the wide range of possibilities of using CADD methodologies for the discovery of efficient P-gp inhibitors.
Description
Keywords
Computer-assisted drug design Homology modeling P-glycoprotein inhibitors Pharmacophore Quantitative structure-activity relationships Structure-based drug design . Faculdade de Ciências Exatas e da Engenharia
Citation
Palmeira, A., Sousa, E., Helena Vasconcelos, M., Pinto, M., & X Fernandes, M. (2012). Structure and ligand-based design of P-glycoprotein inhibitors: a historical perspective. Current pharmaceutical design, 18(27), 4197-4214.
Publisher
Bentham Science Publishers