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

Detalhes bibliográficos
Autor(a) principal: Palmeira, Andreia
Data de Publicação: 2012
Outros Autores: Sousa, Emilia, Vasconcelos, M. Helena, Pinto, Madalena, Fernandes, Miguel X.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.13/5019
Resumo: 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.
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spelling Structure and ligand-based design of P-glycoprotein inhibitors: a historical perspectiveComputer-assisted drug designHomology modelingP-glycoprotein inhibitorsPharmacophoreQuantitative structure-activity relationshipsStructure-based drug design.Faculdade de Ciências Exatas e da EngenhariaComputer-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.Bentham Science PublishersDigitUMaPalmeira, AndreiaSousa, EmiliaVasconcelos, M. HelenaPinto, MadalenaFernandes, Miguel X.2023-02-09T11:08:09Z20122012-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.13/5019engPalmeira, 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), 4197-4214.10.2174/138161212802430530info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-02-12T03:31:06Zoai:digituma.uma.pt:10400.13/5019Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:46:29.745957Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Structure and ligand-based design of P-glycoprotein inhibitors: a historical perspective
title Structure and ligand-based design of P-glycoprotein inhibitors: a historical perspective
spellingShingle Structure and ligand-based design of P-glycoprotein inhibitors: a historical perspective
Palmeira, Andreia
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
title_short Structure and ligand-based design of P-glycoprotein inhibitors: a historical perspective
title_full Structure and ligand-based design of P-glycoprotein inhibitors: a historical perspective
title_fullStr Structure and ligand-based design of P-glycoprotein inhibitors: a historical perspective
title_full_unstemmed Structure and ligand-based design of P-glycoprotein inhibitors: a historical perspective
title_sort Structure and ligand-based design of P-glycoprotein inhibitors: a historical perspective
author Palmeira, Andreia
author_facet Palmeira, Andreia
Sousa, Emilia
Vasconcelos, M. Helena
Pinto, Madalena
Fernandes, Miguel X.
author_role author
author2 Sousa, Emilia
Vasconcelos, M. Helena
Pinto, Madalena
Fernandes, Miguel X.
author2_role author
author
author
author
dc.contributor.none.fl_str_mv DigitUMa
dc.contributor.author.fl_str_mv Palmeira, Andreia
Sousa, Emilia
Vasconcelos, M. Helena
Pinto, Madalena
Fernandes, Miguel X.
dc.subject.por.fl_str_mv 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
topic 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
description 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.
publishDate 2012
dc.date.none.fl_str_mv 2012
2012-01-01T00:00:00Z
2023-02-09T11:08:09Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.13/5019
url http://hdl.handle.net/10400.13/5019
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 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.
10.2174/138161212802430530
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Bentham Science Publishers
publisher.none.fl_str_mv Bentham Science Publishers
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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