title: A 100K well screen for a muscarinic receptor using the Epic label-free system--a reflection on the benefits of the label-free approach to screening seven-transmembrane receptors.
abstract: Seven-transmembrane receptors (7TMRs) are a family of proteins of great interest as therapeutic targets because of their abundance on the cell surface, diverse effects in modulating cell behavior and success as a key class of drugs. We have evaluated the Epic label-free system for the purpose of identifying antagonists of the muscarinic M3 receptor. We compared the data generated from the label-free technology with data for the same compounds in a calcium flux assay. We have shown that this technology can be used for high throughput screening (HTS) of 7TMRs and as an orthogonal approach to enable rapid evaluation of HTS outputs. A number of compounds have been identified which were not found in a functional HTS measuring the output from a single pathway, which may offer new approaches to inhibiting responses through this receptor.
authors.affiliation: Bioscience Department, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leicestershire LE11 5RH, UK. kathryn.dodgson@astrazeneca.com
authors.forename: K
authors.initials: K
authors.lastname: Dodgson
authors.forename: L
authors.initials: L
authors.lastname: Gedge
authors.forename: D C
authors.initials: DC
authors.lastname: Murray
authors.forename: M
authors.initials: M
authors.lastname: Coldwell
mesh_terms: D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004353:Drug Evaluation, Preclinical / Q000379:methods; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000302:isolation & purification* / Q000494:pharmacology; D043587:Receptor, Muscarinic M3 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D018721:Muscarinic Agonists; D043587:Receptor, Muscarinic M3; D043562:Receptors, G-Protein-Coupled; C450520:seven-transmembrane G-protein-coupled receptor; D016210:Methacholine Chloride