Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse agonist

Chaela Presley, Ammaar Abidi, Satyendra Suryawanshi, Suni Mustafa, Bernd Meibohm, Bob Moore

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere00159
JournalPharmacology Research and Perspectives
Volume3
Issue number4
DOIs
StatePublished - Aug 1 2015

Fingerprint

Cannabinoid Receptors
Neurodegenerative Diseases
Brain Concussion
Cannabinoid Receptor Agonists
Microglia
Chemokines
Autoimmune Diseases
SMM-189
Ligands

All Science Journal Classification (ASJC) codes

  • Neurology
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse agonist. / Presley, Chaela; Abidi, Ammaar; Suryawanshi, Satyendra; Mustafa, Suni; Meibohm, Bernd; Moore, Bob.

In: Pharmacology Research and Perspectives, Vol. 3, No. 4, e00159, 01.08.2015.

Research output: Contribution to journalArticle

@article{0fd9240af18f4e369c0a5a592b7e1bf1,
title = "Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse agonist",
abstract = "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.",
author = "Chaela Presley and Ammaar Abidi and Satyendra Suryawanshi and Suni Mustafa and Bernd Meibohm and Bob Moore",
year = "2015",
month = "8",
day = "1",
doi = "10.1002/prp2.159",
language = "English (US)",
volume = "3",
journal = "Pharmacology Research and Perspectives",
issn = "2052-1707",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "4",

}

TY - JOUR

T1 - Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse agonist

AU - Presley, Chaela

AU - Abidi, Ammaar

AU - Suryawanshi, Satyendra

AU - Mustafa, Suni

AU - Meibohm, Bernd

AU - Moore, Bob

PY - 2015/8/1

Y1 - 2015/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84997537532&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84997537532&partnerID=8YFLogxK

U2 - 10.1002/prp2.159

DO - 10.1002/prp2.159

M3 - Article

VL - 3

JO - Pharmacology Research and Perspectives

JF - Pharmacology Research and Perspectives

SN - 2052-1707

IS - 4

M1 - e00159

ER -