title: Discovery of a novel selective kappa-opioid receptor agonist using crystal structure-based virtual screening.
abstract: Kappa-opioid (KOP) receptor agonists exhibit analgesic effects without activating reward pathways. In the search for nonaddictive opioid therapeutics and novel chemical tools to study physiological functions regulated by the KOP receptor, we screened in silico its recently released inactive crystal structure. A selective novel KOP receptor agonist emerged as a notable result and is proposed as a new chemotype for the study of the KOP receptor in the etiology of drug addiction, depression, and/or pain.
authors: Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai , New York, New York 10029, United States.
authors: Ana
authors: A
authors: Negri
authors: Marie-Laure
authors: ML
authors: Rives
authors: Michael J
authors: MJ
authors: Caspers
authors: Thomas E
authors: TE
authors: Prisinzano
authors: Jonathan A
authors: JA
authors: Javitch
authors: Marta
authors: M
authors: Filizola
mesh_terms: D019393:Arrestin / Q000378:metabolism; D018360:Crystallography, X-Ray; D000242:Cyclic AMP / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D016208:Databases, Factual; D055808:Drug Discovery / Q000379:methods*; D019204:GTP-Binding Proteins / Q000378:metabolism; D005822:Genetic Vectors; D057809:HEK293 Cells; D057166:High-Throughput Screening Assays; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000235:genetics; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014162:Transfection; D014584:User-Computer Interface
chemical_list: D019393:Arrestin; D018076:DNA, Complementary; D017473:Receptors, Opioid, kappa; D000242:Cyclic AMP; D019204:GTP-Binding Proteins