title: Use of the X-ray structure of the beta2-adrenergic receptor for drug discovery. Part 2: Identification of active compounds.
abstract: The recently published X-ray structures of the beta(2)-adrenergic receptor are the first examples of ligand-mediated GPCR crystal structures. We have previously performed computational studies that examine the potential viability of these structures for use in drug design, exploiting known ligand activities. Our previous study and a newly reported beta(2)/Timolol X-ray complex provide validation of the computational approaches. In the present work, we use the X-ray structures to extract, via in silico high-throughput docking, compounds from proprietary and commercial databases and demonstrate the successful identification of active compounds by radioligand binding.
authors.affiliation: Lundbeck Research USA, 215 College Road, Paramus, NJ 07652-1431, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Sabio
authors.forename: Kenneth
authors.initials: K
authors.lastname: Jones
authors.forename: Sid
authors.initials: S
authors.lastname: Topiol
mesh_terms: D001665:Binding Sites; D002227:Carbazoles / Q000737:chemistry; D000077261:Carvedilol; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018360:Crystallography, X-Ray / Q000379:methods*; D015195:Drug Design; D055808:Drug Discovery; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D010433:Pentylenetetrazole / Q000737:chemistry; D011412:Propanolamines / Q000737:chemistry; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry*; D014965:X-Rays
chemical_list: D002227:Carbazoles; D008024:Ligands; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D000077261:Carvedilol; D010433:Pentylenetetrazole