Nat Commun. 2017 Jan 3;8:13958. doi: 10.1038/ncomms13958.
Soethoudt M1,2, Grether U3, Fingerle J4, Grim TW5, Fezza F6,7, de Petrocellis L8, Ullmer C3, Rothenhäusler B3, Perret C3, van Gils N2, Finlay D9, MacDonald C9, Chicca A10, Gens MD10, Stuart J11, de Vries H2, Mastrangelo N12, Xia L2, Alachouzos G1, Baggelaar MP1, Martella A1,2, Mock ED1, Deng H1, Heitman LH2, Connor M11, Di Marzo V8, Gertsch J10, Lichtman AH5, Maccarrone M7,12, Pacher P13, Glass M9, van der Stelt M1.
Abstract
The cannabinoid CB2 receptor (CB2R) 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 CB2R, 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 CB2R 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 CB2R agonists to study the role of CB2R 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.
- PMID: 28045021
- DOI: 10.1038/ncomms13958
- [PubMed – in process]
