title: G Protein-Coupled Receptors - Targets for Fragment-based Drug Discovery.
abstract: As the considerable technical challenges involved with generating crystal structures of G (guanine nucleotide- binding) protein-coupled receptors (GPCRs) are starting to be successfully addressed, opportunities to apply fragment-based drug discovery (FBDD) to this class of target are becoming a reality. GPCRs represent a large and important family of drug targets with considerable clinical and commercial interest. While their general seven transmembrane helix bundle structures are amenable to therapeutic intervention with small molecules, to date successful drugs have primarily been discovered using traditional competitive or function-based screening. With advances in biophysical screening techniques such as Surface Plasmon Resonance (SPR) and Target-Immobilised NMR Screening (TINS), being matched to developments in molecular dynamics simulations, virtual screening and stabilisation of biologically relevant conformations of GPCRs, structure-based approaches using fragment starting points are beginning to be applied to the discovery of new generations of small molecules.
authors.affiliation: Structural Biology, UCB, 216 Bath Road, Slough. SL1 3WE UK. alastair.lawson@ucb.com.
authors.forename: Alastair D G
authors.initials: AD
authors.lastname: Lawson
mesh_terms: D055808:Drug Discovery; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D020349:Surface Plasmon Resonance
chemical_list: D043562:Receptors, G-Protein-Coupled