title: 3D-pharmacophore identification for kappa-opioid agonists using ligand-based drug-design techniques.
abstract: A selective kappa-opioid receptor (KOR) agonist might act as a powerful analgesic without the side effects of micro-opioid receptor-selective drugs such as morphine. The eight classes of known KOR agonists have different chemical structures, making it difficult to construct a pharmacophore model that takes them all into account. Here, we summarize previous efforts to identify the pharmacophore for kappa-opioid agonists and propose a new three-dimensional pharmacophore model that encompasses the kappa-activities of all classes. This utilizes conformational sampling of agonists by high-temperature molecular dynamics and pharmacophore extraction through a series of molecular superpositions.
authors.affiliation: School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. yamaotsun@pharm.kitasato-u.ac.jp
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Yamaotsu
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hirono
mesh_terms: D015195:Drug Design; D021621:Imaging, Three-Dimensional; D008024:Ligands; D008958:Models, Molecular; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D017473:Receptors, Opioid, kappa