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

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; ... (2017). Cannabinoid CB2 receptor ligand profiling reveals biased signalling and off-target activity. Nature communications, 8(13958), p. 13958. Nature Publishing Group 10.1038/ncomms13958

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Chicca, Andrea and Gertsch, Jürg

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Barbara Järmann-Bangerter

Date Deposited:

17 Jul 2017 15:13

Last Modified:

08 Sep 2017 17:01

Publisher DOI:

10.1038/ncomms13958

PubMed ID:

28045021

BORIS DOI:

10.7892/boris.94093

URI:

https://boris.unibe.ch/id/eprint/94093

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