Drugs targeting G protein-coupled receptors (GPCRs) make up more than 25% of all prescribed medications. The ability of GPCRs to form heteromers with unique signaling properties may be a new drug target. However, current in vitro assays are ill-equipped to detect heteromer-selective compounds. The present study describes the adaptation of an approach by using fusion proteins of GPCRs and chimeric G proteins to create an in vitro screening assay in which large numbers of compounds can be screened and only activated heteromers are detectable. This assay revealed that the δ-opioid receptor agonist ADL5859 [N,N-diethyl-4-(5-hydroxyspiro[chromene-2,4′-piperidine]-4-yl)benzamide] has a 10-fold higher potency on δ-opioid receptors homomers than δ/μ-opioid receptor heteromers.
See article at J Pharmacol Exp Ther 2013, 344:179–188.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics