title: New concepts in drug discovery: collateral efficacy and permissive antagonism.
abstract: New perspectives on the complexity of G-protein-coupled receptor (GPCR) signalling and the increased resolution of existing tools for studying GPCR behaviour has led to the conception of new hypotheses that affect the discovery of drugs acting at GPCRs. Taking into consideration the novel concepts of collateral efficacy and permissive antagonism in the search for synthetic agonists and antagonists, respectively, will be essential in the search for drugs with unique therapeutic profiles. Here, the design of drugs against HIV is used as an example of how these concepts might be taken into consideration for GPCR-targeted drugs in general.
authors.affiliation: GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, North Carolina 27709, USA. Terry.P.Kenakin@gsk.com
authors.forename: Terry
authors.initials: T
authors.lastname: Kenakin
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D015195:Drug Design; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled