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Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse agonist
Cannabinoid receptor 2 agonists and inverse agonists are emerging as new therapeutic options for a spectrum of autoimmune-related disease. Of particular interest, is the ability of CB2 ligands to regulate microglia function in neurodegenerative diseases and traumatic brain injury. We have previously...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506688/ https://www.ncbi.nlm.nih.gov/pubmed/26196013 http://dx.doi.org/10.1002/prp2.159 |
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author | Presley, Chaela Abidi, Ammaar Suryawanshi, Satyendra Mustafa, Suni Meibohm, Bernd Moore, Bob M |
author_facet | Presley, Chaela Abidi, Ammaar Suryawanshi, Satyendra Mustafa, Suni Meibohm, Bernd Moore, Bob M |
author_sort | Presley, Chaela |
collection | PubMed |
description | Cannabinoid receptor 2 agonists and inverse agonists are emerging as new therapeutic options for a spectrum of autoimmune-related disease. Of particular interest, is the ability of CB2 ligands to regulate microglia function in neurodegenerative diseases and traumatic brain injury. We have previously reported the receptor affinity of 3′,5′-dichloro-2,6-dihydroxy-biphenyl-4-yl)-phenyl-methanone (SMM-189) and the characterization of the beneficial effects of SMM-189 in the mouse model of mild traumatic brain injury. Herein, we report the further characterization of SMM-189 as a potent and selective CB2 inverse agonist, which acts as a noncompetitive inhibitor of CP 55,940. The ability of SMM-189 to regulate microglial activation, in terms of chemokine expression and cell morphology, has been determined. Finally, we have determined that SMM-189 possesses acceptable biopharmaceutical properties indicating that the triaryl class of CB2 inverse agonists are viable compounds for continued preclinical development for the treatment of neurodegenerative disorders and traumatic brain injury. |
format | Online Article Text |
id | pubmed-4506688 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley & Sons, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-45066882015-07-20 Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse agonist Presley, Chaela Abidi, Ammaar Suryawanshi, Satyendra Mustafa, Suni Meibohm, Bernd Moore, Bob M Pharmacol Res Perspect Original Articles Cannabinoid receptor 2 agonists and inverse agonists are emerging as new therapeutic options for a spectrum of autoimmune-related disease. Of particular interest, is the ability of CB2 ligands to regulate microglia function in neurodegenerative diseases and traumatic brain injury. We have previously reported the receptor affinity of 3′,5′-dichloro-2,6-dihydroxy-biphenyl-4-yl)-phenyl-methanone (SMM-189) and the characterization of the beneficial effects of SMM-189 in the mouse model of mild traumatic brain injury. Herein, we report the further characterization of SMM-189 as a potent and selective CB2 inverse agonist, which acts as a noncompetitive inhibitor of CP 55,940. The ability of SMM-189 to regulate microglial activation, in terms of chemokine expression and cell morphology, has been determined. Finally, we have determined that SMM-189 possesses acceptable biopharmaceutical properties indicating that the triaryl class of CB2 inverse agonists are viable compounds for continued preclinical development for the treatment of neurodegenerative disorders and traumatic brain injury. John Wiley & Sons, Ltd 2015-08 2015-07-06 /pmc/articles/PMC4506688/ /pubmed/26196013 http://dx.doi.org/10.1002/prp2.159 Text en © 2015 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Presley, Chaela Abidi, Ammaar Suryawanshi, Satyendra Mustafa, Suni Meibohm, Bernd Moore, Bob M Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse agonist |
title | Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse agonist |
title_full | Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse agonist |
title_fullStr | Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse agonist |
title_full_unstemmed | Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse agonist |
title_short | Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse agonist |
title_sort | preclinical evaluation of smm-189, a cannabinoid receptor 2-specific inverse agonist |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506688/ https://www.ncbi.nlm.nih.gov/pubmed/26196013 http://dx.doi.org/10.1002/prp2.159 |
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