Use of the X-ray structure of the Beta2-adrenergic receptor for drug discovery

Bioorg Med Chem Lett. 2008 Mar 1;18(5):1598-602. doi: 10.1016/j.bmcl.2008.01.063. Epub 2008 Jan 19.

Abstract

The recently reported X-ray structure of the Beta2-adrenergic receptor, the first reported crystal structure of a ligand-mediated GPCR, is used to explore its utility in computer-aided drug design. Validations were conducted with known beta blockers. This was followed by high-throughput docking studies with proprietary and commercial databases to further validate the X-ray structure's usefulness as a design tool and to explore the potential for discovery of novel chemical classes acting as Beta2 inhibitors. Our results include the finding of ligands with traditional beta-blocker motifs as well as new motifs, thereby serving to both validate the approach and project its usefulness in the finding and design of novel compounds.

MeSH terms

  • Adrenergic beta-Agonists / chemistry*
  • Adrenergic beta-Agonists / pharmacology*
  • Adrenergic beta-Antagonists / chemistry*
  • Adrenergic beta-Antagonists / pharmacology*
  • Binding Sites
  • Crystallography, X-Ray
  • Models, Molecular
  • Molecular Structure
  • Receptors, Adrenergic, beta-2 / chemistry*

Substances

  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Receptors, Adrenergic, beta-2