Collybolide is a novel biased agonist of κ-opioid receptors with potent antipruritic activity
Abstract
In recent years, the κ-opioid receptor (κOR) has become an attractive therapeutic target for the treatment of a number of disorders including depression, visceral pain, and drug addiction. A search for natural products with novel scaffolds targeting κOR has been intensive. Here, we report the discovery of a natural product (Colly) from the fungus Collybia maculata as a novel scaffold that contains a furyl-δ-lactone core structure similar to that of Salvinorin A, another natural product isolated from the mint Salvia divinorum. We show that Colly functions as a κOR agonist with antinociceptive and antipruritic activity. Interestingly, Colly exhibits biased agonistic activity, suggesting that it could be used as a backbone for the generation of novel therapeutics targeting κOR with reduced side effects.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- May 2016
- DOI:
- 10.1073/pnas.1521825113
- Bibcode:
- 2016PNAS..113.6041G