Structure and Ligand-based Design of P-glycoprotein Inhibitors: A Historical Perspective

• Tipo: Outra Publicação em Revista Científica Internacional
• Data: 2012

Autores

Andreia Palmeira (Autor) Outra; Emilia Sousa (Autor) FFUP; Helena Vasconcelos, MH (Autor) FFUP; Madalena Pinto (Autor) FFUP; Miguel X Fernandes (Autor) Outra

Revista

Título: Current Pharmaceutical Design

Vol. 18

Páginas: 4197-4214

ISSN: 1381-6128

Editora: Bentham Science

Indexação

ISI Proceedings

ISI Web of Knowledge - 38 Citações

Scopus - 39 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

Outras Informações

ID Authenticus: P-002-6K2

DOI: 10.2174/138161212802430530

Abstract (EN): 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 pharmacophore 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 18