title: Identification of the three-dimensional pharmacophore of kappa-opioid receptor agonists.
abstract: A selective kappa-opioid receptor agonist might act as a powerful analgesic without the side effects of mu-opioid receptor-selective drugs such as morphine. The eight classes of known kappa-opioid receptor agonists have different chemical structures, making it difficult to construct a pharmacophore model that takes them all into account. Here we propose a new three-dimensional pharmacophore model that encompasses the kappa-activities of all classes, which 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, Minato-ku, Tokyo 108-8641, Japan. yamaotsun@pharm.kitasato-u.ac.jp
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Yamaotsu
authors.forename: Hideaki
authors.initials: H
authors.lastname: Fujii
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagase
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hirono
mesh_terms: D008956:Models, Chemical; D008958:Models, Molecular; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000378:metabolism
chemical_list: D017473:Receptors, Opioid, kappa