title: CJ-15,208, a novel kappa opioid receptor antagonist from a fungus, Ctenomyces serratus ATCC15502.
abstract: A novel kappa opioid receptor binding inhibitor CJ-15,208 (I) was isolated from the fermentation broth of a fungus, Ctenomyces serratus ATCC15502. The structure of I was determined to be a cyclic tetrapeptide consisting of one tryptophan, one D-proline, and two L-phenylalanine. Compound I was a selective binding inhibitor for the kappa opioid receptor: 47 nM (IC50) for kappa, 260 nM for mu, and 2,600 nM for delta. In the electrically-stimulated twitch response assay of rabbit vas deferens I recovered the suppression by a kappa agonist asimadoline with an ED50 of 1.3 microM, indicating that it is a kappa antagonist.
authors.affiliation: Exploratory Medicinal Sciences, PGRD, Nagoya Laboratories, Pfizer Pharmaceuticals, Inc., 5-2, Taketoyo-cho, Chita-gun, Aichi 470-2393, Japan. Toshiyuki.Saito@japan.pfizer.com
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Saito
authors.forename: Hideo
authors.initials: H
authors.lastname: Hirai
authors.forename: Yoon-Jeong
authors.initials: YJ
authors.lastname: Kim
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kojima
authors.forename: Yasue
authors.initials: Y
authors.lastname: Matsunaga
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishida
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Sakakibara
authors.forename: Osamu
authors.initials: O
authors.lastname: Suga
authors.forename: Tetsujo
authors.initials: T
authors.lastname: Sujaku
authors.forename: Nakao
authors.initials: N
authors.lastname: Kojima
mesh_terms: D000818:Animals; D003883:Arthrodermataceae; D004558:Electric Stimulation; D005285:Fermentation; D006168:Guinea Pigs; D008297:Male; D009292:Narcotic Antagonists / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D011817:Rabbits; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects
chemical_list: D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa