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-proline, and two L-phenylalanine. Compound I was a selective binding inhibitor for the κ opioid receptor: 47 nM (IC50) for κ, 260 nM for μ, and 2,600 nM 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 1.3 μM, indicating that it is a κ antagonist.