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.
Publication types
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Letter
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Research Support, N.I.H., Extramural
MeSH terms
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Arrestin / metabolism
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Crystallography, X-Ray
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Cyclic AMP / metabolism
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DNA, Complementary / biosynthesis
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DNA, Complementary / genetics
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Databases, Factual
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Drug Discovery / methods*
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GTP-Binding Proteins / metabolism
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Genetic Vectors
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HEK293 Cells
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High-Throughput Screening Assays
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Humans
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Models, Molecular
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Molecular Conformation
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Receptors, Opioid, kappa / agonists*
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Receptors, Opioid, kappa / genetics
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Stereoisomerism
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Structure-Activity Relationship
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Transfection
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User-Computer Interface
Substances
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Arrestin
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DNA, Complementary
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Receptors, Opioid, kappa
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Cyclic AMP
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GTP-Binding Proteins