Virtual screening of novel CB2 ligands using a comparative model of the human cannabinoid CB2 receptor.
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.
Salo
Outi M H
OM
Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. outi.salo@uku.fi
Raitio
Katri H
KH
Savinainen
Juha R
JR
Nevalainen
Tapio
T
Lahtela-Kakkonen
Maija
M
Laitinen
Jarmo T
JT
Järvinen
Tomi
T
Poso
Antti
A
D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002417:Cattle; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D008958:Models, Molecular; D011487:Protein Conformation; D011869:Radioligand Assay; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000737:chemistry* / Q000235:genetics; D012243:Rhodopsin / Q000737:chemistry
C507022:1-isoquinolyl-(3-(trifluoromethyl)phenyl)methanone; D007546:Isoquinolines; D008024:Ligands; D043885:Receptor, Cannabinoid, CB2; D012243:Rhodopsin