ArticleMolecular pharmacology2014
Identification of novel functionally selective κ-opioid receptor scaffolds.
Article in Molecular pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
71 citing papers in PubMed, 139 citations in OpenAlex.
- Opioid Receptors in Psychedelia: Indirect Serotonergic Modulation of Direct KOR Activation by Salvinorin A.Biomedicines · 2026Review
- Agonism and Biased Signaling.Handbook of experimental pharmacology · 2026Review
- The structural diversity of psychedelic drug actions revealed.Nature communications · 2025Article
- Limitations and potential of κOR biased agonists for pain and itch management.Neuropharmacology · 2024Review
- Know your molecule: pharmacological characterization of drug candidates to enhance efficacy and reduce late-stage attrition.Nature reviews. Drug discovery · 2024Review
- Dopamine DNeuroscience · 2024Article
- Structure-function relationship of dynorphin B variants using naturally occurring amino acid substitutions.Frontiers in pharmacology · 2024Article
- From Plant to Chemistry: Sources of Active Opioid Antinociceptive Principles for Medicinal Chemistry and Drug Design.Molecules (Basel, Switzerland) · 2023Review
- Development of a Selective Peptide κ-Opioid Receptor Antagonist by Late-Stage Functionalization with Cysteine Staples.Journal of medicinal chemistry · 2023Article
- Opioid signaling and design of analgesics.Progress in molecular biology and translational science · 2023Review
- Mind the Gap-Deciphering GPCR Pharmacology Using 3D Pharmacophores and Artificial Intelligence.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Evaluation of the Intracellular Signaling Activities of κ-Opioid Receptor Agonists, Nalfurafine Analogs; Focusing on the Selectivity of G-Protein- and β-Arrestin-Mediated Pathways.Molecules (Basel, Switzerland) · 2022Article
- Community guidelines for GPCR ligand bias: IUPHAR review 32.British journal of pharmacology · 2022Review
- Quantitative Systems Pharmacology and Biased Agonism at Opioid Receptors: A Potential Avenue for Improved Analgesics.International journal of molecular sciences · 2022Review
- An updated assessment of the translational promise of G-protein-biased kappa opioid receptor agonists to treat pain and other indications without debilitating adverse effects.Pharmacological research · 2022Review
- Agonist-Promoted Phosphorylation and Internalization of the Kappa Opioid Receptor in Mouse Brains: Lack of Connection With Conditioned Place Aversion.Frontiers in pharmacology · 2022Article
- Signaling underlying kappa opioid receptor-mediated behaviors in rodents.Frontiers in neuroscience · 2022Review
- Pharmacology of Kappa Opioid Receptors: Novel Assays and Ligands.Frontiers in pharmacology · 2022Article
- Kappa Opioid Receptor Ligands and Pharmacology: Diphenethylamines, a Class of Structurally Distinct, Selective Kappa Opioid Ligands.Handbook of experimental pharmacology · 2022Review
- Antinociceptive Effects of Kappa-Opioid Receptor Agonists.Handbook of experimental pharmacology · 2022Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
The κ-opioid receptor (KOR)-dynorphin system has been implicated in the control of affect, cognition, and motivation, and is thought to be dysregulated in mood and psychotic disorders, as well as in various phases of opioid dependence. KOR agonists exhibit analgesic effects, although the adverse effects produced by some KOR agonists, including sedation, dysphoria, and hallucinations, have limited their clinical use. Interestingly, KOR-mediated dysphoria, assessed in rodents as aversion, has recently been attributed to the activation of the p38 mitogen-activated protein kinase pathway following arrestin recruitment to the activated KOR. Therefore, KOR-selective G protein-biased agonists, which do not recruit arrestin, have been proposed to be more effective analgesics, without the adverse effects triggered by the arrestin pathway. As an initial step toward identifying novel biased KOR agonists, we applied a multifaceted screening strategy utilizing both in silico and parallel screening approaches. We identified several KOR-selective ligand scaffolds with a range of signaling bias in vitro. The arylacetamide-based scaffold includes both G protein- and β-arrestin-biased ligands, while the endogenous peptides and the diterpene scaffolds are G protein biased. Interestingly, we found scaffold screening to be more successful than library screening in identifying biased ligands. Many of the identified functionally selective ligands are potent selective KOR agonists that are reported to be active in the central nervous system. They therefore represent excellent candidates for in vivo studies aiming at determining the behavioral effects mediated by specific KOR-mediated signaling cascades.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.