Identification of the three-dimensional pharmacophore of kappa-opioid receptor agonists.
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.
Yamaotsu
Noriyuki
N
School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan. yamaotsun@pharm.kitasato-u.ac.jp
Fujii
Hideaki
H
Nagase
Hiroshi
H
Hirono
Shuichi
S
D008956:Models, Chemical; D008958:Models, Molecular; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000378:metabolism
D017473:Receptors, Opioid, kappa