Impact of the Recent Mouse P-Glycoprotein Structure for Structure-Based Ligand Design

Freya Klepsch; Gerhard F Ecker

doi:10.1002/minf.201000017

Impact of the Recent Mouse P-Glycoprotein Structure for Structure-Based Ligand Design

Mol Inform. 2010 Apr 12;29(4):276-86. doi: 10.1002/minf.201000017. Epub 2010 Apr 20.

Authors

Freya Klepsch¹, Gerhard F Ecker²

Affiliations

¹ University of Vienna, Department of Medicinal Chemistry, Althanstraße 14, 1090 Wien, Austria phone: +43-1-4277-55110; fax: +43-1-4277-9551.
² University of Vienna, Department of Medicinal Chemistry, Althanstraße 14, 1090 Wien, Austria phone: +43-1-4277-55110; fax: +43-1-4277-9551. Gerhard.f.ecker@univie.ac.at.

Abstract

P-Glycoprotein (P-gp), a transmembrane, ATP-dependent drug efflux transporter, has attracted considerable interest both with respect to its role in tumour cell multidrug resistance and in absorption-distribution and elimination of drugs. Although known since more than 30 years, the understanding of the molecular basis of drug/transporter interaction is still limited, which is mainly due to the lack of structural information available. However, within the past decade X-ray structures of several bacterial homologues as well as very recently also of mouse P-gp have become available. Within this review we give an overview on the current status of structural information available and on its impact for structure-based drug design.

Keywords: Drug design, Ligands; Molecular modelling; Proteins.

Publication types

Review

Grants and funding

F 3502/FWF_/Austrian Science Fund FWF/Austria