Portal de Periódicos da CAPES

Cannabinoid CB2 receptor ligand profiling reveals biased signalling and off-target activity

2017; Nature Portfolio; Volume: 8; Issue: 1 Linguagem: Inglês

10.1038/ncomms13958

2041-1723

Marjolein Soethoudt, Uwe Grether, Jürgen Fingerle, Travis W. Grim, Filomena Fezza, Luciano De Petrocellis, Christoph Ullmer, Benno Rothenhäusler, Camille Perret, Noortje van Gils, David B. Finlay, Christa MacDonald, Andrea Chicca, Marianela Dalghi Gens, Jordyn Stuart, Henk de Vries, Nicolina Mastrangelo, Lizi Xia, Georgios Alachouzos, Marc P. Baggelaar, Andrea Martella, Elliot D. Mock, Hui Deng, Laura H. Heitman, Mark Connor, Vincenzo Di Marzo, Jürg Gertsch, Aron H. Lichtman, Mauro Maccarrone, Pál Pacher, Michelle Glass, Mario van der Stelt,

Pharmacological Receptor Mechanisms and Effects

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.