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

Marjolein Soethoudt, Uwe Grether, Jürgen Fingerle, Travis W. Grim, Filomena Fezza, Luciano de Petrocellis, Christoph Ullmer, Benno Rothenhäusler, Camille Perret, Noortje van Gils, David 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, Pal Pacher (), Michelle Glass () and Mario van der Stelt ()
Additional contact information
Marjolein Soethoudt: Leiden Institute of Chemistry, Leiden University
Uwe Grether: Roche Innovation Center Basel, F. Hoffman-La Roche Ltd.
Jürgen Fingerle: NMI, University Tübingen
Travis W. Grim: Department of Pharmacology and Toxicology
Filomena Fezza: Tor Vergata University of Rome
Luciano de Petrocellis: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, C.N.R.
Christoph Ullmer: Roche Innovation Center Basel, F. Hoffman-La Roche Ltd.
Benno Rothenhäusler: Roche Innovation Center Basel, F. Hoffman-La Roche Ltd.
Camille Perret: Roche Innovation Center Basel, F. Hoffman-La Roche Ltd.
Noortje van Gils: Leiden Academic Centre for Drug Research, Leiden University
David Finlay: Faculty of Medical and Health Sciences, University of Auckland
Christa MacDonald: Faculty of Medical and Health Sciences, University of Auckland
Andrea Chicca: Institute of Biochemistry and Molecular Medicine, University of Bern
Marianela Dalghi Gens: Institute of Biochemistry and Molecular Medicine, University of Bern
Jordyn Stuart: Faculty of Medicine and Health Sciences, Macquarie University, North Ryde
Henk de Vries: Leiden Academic Centre for Drug Research, Leiden University
Nicolina Mastrangelo: Campus Bio-Medico University of Rome
Lizi Xia: Leiden Academic Centre for Drug Research, Leiden University
Georgios Alachouzos: Leiden Institute of Chemistry, Leiden University
Marc P. Baggelaar: Leiden Institute of Chemistry, Leiden University
Andrea Martella: Leiden Institute of Chemistry, Leiden University
Elliot D. Mock: Leiden Institute of Chemistry, Leiden University
Hui Deng: Leiden Institute of Chemistry, Leiden University
Laura H. Heitman: Leiden Academic Centre for Drug Research, Leiden University
Mark Connor: Faculty of Medicine and Health Sciences, Macquarie University, North Ryde
Vincenzo Di Marzo: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, C.N.R.
Jürg Gertsch: Institute of Biochemistry and Molecular Medicine, University of Bern
Aron H. Lichtman: Department of Pharmacology and Toxicology
Mauro Maccarrone: European Center for Brain Research/IRCCS Santa Lucia Foundation
Pal Pacher: Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute of Health/NIAAA
Michelle Glass: Faculty of Medical and Health Sciences, University of Auckland
Mario van der Stelt: Leiden Institute of Chemistry, Leiden University

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/ncomms13958 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms13958

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms13958

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().