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Soethoudt, Marjolein; Grether, Uwe; Fingerle, Jürgen; Grim, Travis W.; Fezza, Filomena; de Petrocellis, Luciano; Ullmer, Christoph; Rothenhäusler, Benno; Perret, Camille; van Gils, Noortje; Finlay, David; MacDonald, Christa; Chicca, Andrea; Gens, Marianela Dalghi; Stuart, Jordyn; de Vries, Henk; Mastrangelo, Nicolina; Xia, Lizi; Alachouzos, Georgios; Baggelaar, Marc P.; Martella, Andrea; Mock, Elliot D.; Deng, Hui; Heitman, Laura H.; Connor, Mark; Di Marzo, Vincenzo; Gertsch, Jürg; Lichtman, Aron H.; Maccarrone, Mauro; Pacher, Pal; Glass, Michelle; van der Stelt, Mario
Nature communications, 01/2017, Volume: 8, Issue: 1Journal Article
Abstract The cannabinoid CB 2 receptor (CB 2 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 2 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 2 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 2 R agonists to study the role of CB 2 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.
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