CJ-15, 208, a Novel Kappa Opioid Receptor Antagonist from a Fungus, Ctenomyces serratus ATCC15502

• Published in: Journal of antibiotics 2002/10/25, Vol.55(10), pp.847-854
• Main Authors: SAITO, TOSHIYUKI, HIRAI, HIDEO, KIM, YOON-JEONG, KOJIMA, YASUHIRO, MATSUNAGA, YASUE, NISHIDA, HIROYUKI, SAKAKIBARA, TATSUO, SUGA, OSAMU, SUJAKU, TETSUJO, KOJIMA, NAKAO
• Format: Article
• Language: English
• Subjects: Animals; Arthrodermataceae; Biological and medical sciences; Electric Stimulation; Fermentation; Guinea Pigs; Male; Medical sciences; Narcotic Antagonists - chemistry; Narcotic Antagonists - isolation & purification; Narcotic Antagonists - pharmacology; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Rabbits; Receptors, Opioid, kappa - antagonists & inhibitors; Structure-Activity Relationship; Vas Deferens - drug effects
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.55.847

A novel κ 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-prohne, and two L-phenylalanine. Compound I was a selective binding inhibitor for the κ opioid receptor: 47nM (IC50) for κ, 260nM for μ, and 2, 600nM for δ. In the electrically-stimulated twitch response assay of rabbit vas deferens I recovered the suppression by a κ agonist asimadoline with an ED50 of 1.3μM, indicating that it is a κ antagonist.