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Structure-based discovery of [[beta].sub.2]-adrenergic receptor ligands

Authors :
Kolb, Peter
Rosenbaum, Daniel M.
Irwin, John J.
Fung, Juan Jose
Kobilka, Brian K.
Shoichet, Brian K.
Source :
Proceedings of the National Academy of Sciences of the United States. April 21, 2009, Vol. 106 Issue 16, p6843, 6 p.
Publication Year :
2009

Abstract

Aminergic G protein-coupled receptors (GPCRs) have been a major focus of pharmaceutical research for many years. Due partly to the lack of reliable receptor structures, drug discovery efforts have been largely ligand-based. The recently determined X-ray structure of the [[beta].sub.2]-adrenergic receptor offers an opportunity to investigate the advantages and limitations inherent in a structure-based approach to ligand discovery against this and related GPCR targets. Approximately 1 million commercially available, 'lead-like' molecules were docked against the [[beta].sub.2]-adrenergic receptor structure. On testing of 25 high-ranking molecules, 6 were active with binding affinities docking | GPCR | inverse agonists | library bias | ligand design

Details

Language :
English
ISSN :
00278424
Volume :
106
Issue :
16
Database :
Gale General OneFile
Journal :
Proceedings of the National Academy of Sciences of the United States
Publication Type :
Academic Journal
Accession number :
edsgcl.199396465