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

Abstract

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.