Virtual screening of novel CB2 ligands using a comparative model of the human cannabinoid CB2 receptor

Outi M H Salo; Katri H Raitio; Juha R Savinainen; Tapio Nevalainen; Maija Lahtela-Kakkonen; Jarmo T Laitinen; Tomi Järvinen; Antti Poso

doi:10.1021/jm050565b

Virtual screening of novel CB2 ligands using a comparative model of the human cannabinoid CB2 receptor

J Med Chem. 2005 Nov 17;48(23):7166-71. doi: 10.1021/jm050565b.

Authors

Outi M H Salo¹, Katri H Raitio, Juha R Savinainen, Tapio Nevalainen, Maija Lahtela-Kakkonen, Jarmo T Laitinen, Tomi Järvinen, Antti Poso

Affiliation

¹ Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. outi.salo@uku.fi

PMID: 16279774
DOI: 10.1021/jm050565b

Abstract

To identify novel selective CB2 lead compounds, a comparative model of the CB2 receptor was constructed using the high-resolution bovine rhodopsin X-ray structure as a template. The CB2 model was utilized both in building the database queries and in filtering the hit compounds by a docking and scoring method. In G-protein activation assays, 1-isoquinolyl[3-(trifluoromethyl)phenyl]methanone (40, NRB 04079) was found to act as a selective agonist at the human CB2 receptor.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Binding Sites
CHO Cells
Cattle
Cricetinae
Cricetulus
Humans
Isoquinolines / chemical synthesis
Isoquinolines / chemistry*
Isoquinolines / pharmacology
Ligands
Models, Molecular*
Protein Conformation
Radioligand Assay
Receptor, Cannabinoid, CB2 / agonists*
Receptor, Cannabinoid, CB2 / chemistry*
Receptor, Cannabinoid, CB2 / genetics
Rhodopsin / chemistry

Substances

1-isoquinolyl-(3-(trifluoromethyl)phenyl)methanone
Isoquinolines
Ligands
Receptor, Cannabinoid, CB2
Rhodopsin