Cannabinoid CB<sub>2</sub> receptor ligand profiling reveals biased signalling and off-target activity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28045021.
- Also identified by DOI 10.1038/ncomms13958 and PMC identifier 5216056.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The cannabinoid CB<sub>2</sub> receptor (CB<sub>2</sub>R) represents a promising therapeutic target for various forms of tissue injury and inflammatory diseases. Although numerous compounds have been developed and widely used to target CB<sub>2</sub>R, their selectivity, molecular mode of action and pharmacokinetic properties have been poorly characterized. Here we report the most extensive characterization of the molecular pharmacology of the most widely used CB<sub>2</sub>R ligands to date. In a collaborative effort between multiple academic and industry laboratories, we identify marked differences in the ability of certain agonists to activate distinct signalling pathways and to cause off-target effects. We reach a consensus that HU910, HU308 and JWH133 are the recommended selective CB<sub>2</sub>R agonists to study the role of CB<sub>2</sub>R in biological and disease processes. We believe that our unique approach would be highly suitable for the characterization of other therapeutic targets in drug discovery research.
Medical subject headings
- Cannabinoid Receptor Agonists
- Neurons
- Receptor, Cannabinoid, CB1
- Receptor, Cannabinoid, CB2
- Signal Transduction