ArticleProceedings of the National Academy of Sciences of the United States of America2016
Collybolide is a novel biased agonist of κ-opioid receptors with potent antipruritic activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Semi-synthesis in the exploration of opioid-targeting natural products.Natural product reports · 2025Review
- Morphine-Induced Antinociception Is Potentiated and Dopamine Elevations Are Inhibited by the Biased Kappa Opioid Receptor Agonist Triazole 1.1.ACS chemical neuroscience · 2025Article
- Ketamine and Major Ketamine Metabolites Function as Allosteric Modulators of Opioid Receptors.Molecular pharmacology · 2024Article
- Discovery of Novel, Selective, and Nonbasic Agonists for the Kappa-Opioid Receptor Determined by Salvinorin A-Based Virtual Screening.Journal of medicinal chemistry · 2024Article
- A scoping review of the effects of mushroom and fungus extracts in rodent models of depression and tests of antidepressant activity.Frontiers in pharmacology · 2024Article
- Formal Total Synthesis of Salvinorin A.ChemistryOpen · 2022Article
- Asymmetric Syntheses of (+)- and (-)-Collybolide Enable Reevaluation ofACS central science · 2022Article
- Structural Characterization of KOR Inactive and Active States for 3D Pharmacology and Drug Discovery.Handbook of experimental pharmacology · 2022Review
- Biased Ligands at the Kappa Opioid Receptor: Fine-Tuning Receptor Pharmacology.Handbook of experimental pharmacology · 2022Review
- Kappa Opioid Receptor Ligands and Pharmacology: Diphenethylamines, a Class of Structurally Distinct, Selective Kappa Opioid Ligands.Handbook of experimental pharmacology · 2022Review
- The Kappa Opioid Receptor: A Promising Therapeutic Target for Multiple Pathologies.Frontiers in pharmacology · 2022Review
- Comprehensive overview of biased pharmacology at the opioid receptors: biased ligands and bias factors.RSC medicinal chemistry · 2021Review
- Biosynthesis and synthetic biology of psychoactive natural products.Chemical Society reviews · 2021Review
- Natural Products for the Treatment of Pain: Chemistry and Pharmacology of Salvinorin A, Mitragynine, and Collybolide.Biochemistry · 2021Review
- Compartment-specific opioid receptor signaling is selectively modulated by different dynorphin peptides.eLife · 2021Article
- Controlling opioid receptor functional selectivity by targeting distinct subpockets of the orthosteric site.eLife · 2021Article
- The Role of the Kappa Opioid System in Comorbid Pain and Psychiatric Disorders: Function and Implications.Frontiers in neuroscience · 2021Review
- Antinociceptive and Antipruritic Effects of HSK21542, a Peripherally-Restricted Kappa Opioid Receptor Agonist, in Animal Models of Pain and Itch.Frontiers in pharmacology · 2021Article
- Chemical syntheses of the salvinorin chemotype of KOR agonist.Natural product reports · 2020Review
- Strategies for DevelopingThe Journal of pharmacology and experimental therapeutics · 2020Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Among the opioid receptors, the κ-opioid receptor (κOR) has been gaining considerable attention as a potential therapeutic target for the treatment of complex CNS disorders including depression, visceral pain, and cocaine addiction. With an interest in discovering novel ligands targeting κOR, we searched natural products for unusual scaffolds and identified collybolide (Colly), a nonnitrogenous sesquiterpene from the mushroom Collybia maculata. This compound has a furyl-δ-lactone core similar to that of Salvinorin A (Sal A), another natural product from the plant Salvia divinorum Characterization of the molecular pharmacological properties reveals that Colly, like Sal A, is a highly potent and selective κOR agonist. However, the two compounds differ in certain signaling and behavioral properties. Colly exhibits 10- to 50-fold higher potency in activating the mitogen-activated protein kinase pathway compared with Sal A. Taken with the fact that the two compounds are equipotent for inhibiting adenylyl cyclase activity, these results suggest that Colly behaves as a biased agonist of κOR. Behavioral studies also support the biased agonistic activity of Colly in that it exhibits ∼10-fold higher potency in blocking non-histamine-mediated itch compared with Sal A, and this difference is not seen in pain attenuation by these two compounds. These results represent a rare example of functional selectivity by two natural products that act on the same receptor. The biased agonistic activity, along with an easily modifiable structure compared with Sal A, makes Colly an ideal candidate for the development of novel therapeutics targeting κOR with reduced side effects.
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