CJ-15,208, a novel kappa opioid receptor antagonist from a fungus, Ctenomyces serratus ATCC15502.
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.
Saito
Toshiyuki
T
Exploratory Medicinal Sciences, PGRD, Nagoya Laboratories, Pfizer Pharmaceuticals, Inc., 5-2, Taketoyo-cho, Chita-gun, Aichi 470-2393, Japan. Toshiyuki.Saito@japan.pfizer.com
Hirai
Hideo
H
Kim
Yoon-Jeong
YJ
Kojima
Yasuhiro
Y
Matsunaga
Yasue
Y
Nishida
Hiroyuki
H
Sakakibara
Tatsuo
T
Suga
Osamu
O
Sujaku
Tetsujo
T
Kojima
Nakao
N
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
D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa