Structure and ligand-based design of P-glycoprotein inhibitors: a historical perspective

Palmeira, Andreia; Sousa, Emilia; Vasconcelos, M. Helena; Pinto, Madalena; Fernandes, Miguel X.

Publication

Structure and ligand-based design of P-glycoprotein inhibitors: a historical perspective

2012Journal article

dc.contributor.author	Palmeira, Andreia
dc.contributor.author	Sousa, Emilia
dc.contributor.author	Vasconcelos, M. Helena
dc.contributor.author	Pinto, Madalena
dc.contributor.author	Fernandes, Miguel X.
dc.date.accessioned	2023-02-09T11:08:09Z
dc.date.available	2023-02-09T11:08:09Z
dc.date.issued	2012
dc.description.abstract	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.	pt_PT
dc.description.version	info:eu-repo/semantics/publishedVersion	pt_PT
dc.identifier.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.	pt_PT
dc.identifier.doi	10.2174/138161212802430530	pt_PT
dc.identifier.uri	http://hdl.handle.net/10400.13/5019
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.publisher	Bentham Science Publishers	pt_PT
dc.relation	Strategic Project - UI 4040 - 2011-2012
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/	pt_PT
dc.subject	Computer-assisted drug design	pt_PT
dc.subject	Homology modeling	pt_PT
dc.subject	P-glycoprotein inhibitors	pt_PT
dc.subject	Pharmacophore	pt_PT
dc.subject	Quantitative structure-activity relationships	pt_PT
dc.subject	Structure-based drug design	pt_PT
dc.subject	.	pt_PT
dc.subject	Faculdade de Ciências Exatas e da Engenharia	pt_PT
dc.title	Structure and ligand-based design of P-glycoprotein inhibitors: a historical perspective	pt_PT
dc.type	journal article
dspace.entity.type	Publication
oaire.awardTitle	Strategic Project - UI 4040 - 2011-2012
oaire.awardURI	info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/PEst-OE%2FSAU%2FUI4040%2F2011/PT
oaire.citation.endPage	4214	pt_PT
oaire.citation.issue	27	pt_PT
oaire.citation.startPage	4197	pt_PT
oaire.citation.title	Current Pharmaceutical Design	pt_PT
oaire.citation.volume	18	pt_PT
oaire.fundingStream	6817 - DCRRNI ID
person.familyName	Fernandes
person.givenName	Miguel Xavier
person.identifier.ciencia-id	ED1D-3C7A-467C
person.identifier.orcid	0000-0002-1840-616X
person.identifier.rid	A-4373-2013
person.identifier.scopus-author-id	35466972500
project.funder.identifier	http://doi.org/10.13039/501100001871
project.funder.name	Fundação para a Ciência e a Tecnologia
rcaap.rights	openAccess	pt_PT
rcaap.type	article	pt_PT
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