title: Characterizing cannabinoid CB2 receptor ligands using DiscoveRx PathHunter beta-arrestin assay.
abstract: The authors have characterized a set of cannabinoid CB(2) receptor ligands, including triaryl bis sulfone inverse agonists, in a cell-based receptor/beta-arrestin interaction assay (DiscoveRx PathHunter). The results were compared with results using a competitive ligand binding assay, and with effects on forskolin-stimulated cAMP levels (PerkinElmer LANCE). The authors show good correlation between the 3 assay systems tested, with the beta-arrestin protein complementation assay exhibiting a more robust signal than the cAMP assay for cannabinoid CB(2) agonists. Further assay validation shows that DiscoveRx PathHunter HEK293 CB(2) beta-arrestin assay can be carried out from cryopreserved cell suspensions, eliminating variations caused by the need for multiple cell pools during live cell screening campaigns. These results, and the authors' results evaluating a test set of random library compounds, validate the use of ligand-induced interaction between the human cannabinoid CB(2) receptor and beta-arrestin as an appropriate and valuable screening platform for compounds specific for the cannabinoid CB(2) receptor.
authors.affiliation: New Lead Discovery, Schering-Plough Research Institute, Kenilworth, New Jersey, USA.
authors.forename: Debra
authors.initials: D
authors.lastname: McGuinness
authors.forename: Asra
authors.initials: A
authors.lastname: Malikzay
authors.forename: Richard
authors.initials: R
authors.lastname: Visconti
authors.forename: Karen
authors.initials: K
authors.lastname: Lin
authors.forename: Marvin
authors.initials: M
authors.lastname: Bayne
authors.forename: Frederick
authors.initials: F
authors.lastname: Monsma
authors.forename: Charles A
authors.initials: CA
authors.lastname: Lunn
mesh_terms: D000818:Animals; D019390:Arrestins / Q000032:analysis* / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D006801:Humans; D008024:Ligands; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000378:metabolism*; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D008024:Ligands; D043885:Receptor, Cannabinoid, CB2; D000071557:beta-Arrestins