Discovery of a novel selective kappa-opioid receptor agonist using crystal structure-based virtual screening

J Chem Inf Model. 2013 Mar 25;53(3):521-6. doi: 10.1021/ci400019t. Epub 2013 Mar 13.


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

  • Letter
  • Research Support, N.I.H., Extramural

MeSH terms

  • Arrestin / metabolism
  • Crystallography, X-Ray
  • Cyclic AMP / metabolism
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / genetics
  • Databases, Factual
  • Drug Discovery / methods*
  • GTP-Binding Proteins / metabolism
  • Genetic Vectors
  • HEK293 Cells
  • High-Throughput Screening Assays
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • Receptors, Opioid, kappa / agonists*
  • Receptors, Opioid, kappa / genetics
  • Stereoisomerism
  • Structure-Activity Relationship
  • Transfection
  • User-Computer Interface


  • Arrestin
  • DNA, Complementary
  • Receptors, Opioid, kappa
  • Cyclic AMP
  • GTP-Binding Proteins