Structure-based discovery of beta2-adrenergic receptor ligands.

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(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(2)-adrenergic receptor structure. On testing of 25 high-ranking molecules, 6 were active with binding affinities <4 microM, with the best molecule binding with a K(i) of 9 nM (95% confidence interval 7-10 nM). Five of these molecules we

SUBMITTER: Kolb P 

PROVIDER: S-EPMC2672528 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature