title: An ultra-HTS process for the identification of small molecule modulators of orphan G-protein-coupled receptors.
abstract: G-protein-coupled receptors (GPCRs) are the most successful target proteins for drug discovery research to date. More than 150 orphan GPCRs of potential therapeutic interest have been identified for which no activating ligands or biological functions are known. One of the greatest challenges in the pharmaceutical industry is to link these orphan GPCRs with human diseases. Highly automated parallel approaches that integrate ultra-high throughput and focused screening can be used to identify small molecule modulators of orphan GPCRs. These small molecules can then be employed as pharmacological tools to explore the function of orphan receptors in models of human disease. In this review, we describe methods that utilize powerful ultra-high-throughput screening technologies to identify surrogate ligands of orphan GPCRs.
authors.affiliation: Department of Lead Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492, USA. angela.cacace@bms.com
authors.forename: Angela
authors.initials: A
authors.lastname: Cacace
authors.forename: Martyn
authors.initials: M
authors.lastname: Banks
authors.forename: Timothy
authors.initials: T
authors.lastname: Spicer
authors.forename: Francesca
authors.initials: F
authors.lastname: Civoli
authors.forename: John
authors.initials: J
authors.lastname: Watson
mesh_terms: D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004345:Drug Industry / Q000379:methods / Q000639:trends*; D017930:Genes, Reporter; D008024:Ligands; D008904:Miniaturization; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D001618:beta-Lactamases / Q000235:genetics
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D001618:beta-Lactamases