ArticleNature communications2023
Molecular mechanism of biased signaling at the kappa opioid receptor.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 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.
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Who cites it
53 citing papers in PubMed, 94 citations in OpenAlex.
- Steric control of signaling bias in the immunometabolic receptor GPR84.Nature communications · 2026Article
- Molecular mechanism of allosteric modulation of opioid receptors.Signal transduction and targeted therapy · 2026Article
- Structural characterization of kappa-opioid receptor dimer in complex with two G proteins.Nature communications · 2026Article
- Structural and dynamic studies uncover a distinct allosteric modulatory site at the µ-opioid receptor.Nature communications · 2026Article
- Identification of Subtype-Selective Binding Sites in the Opioid Receptor Family.Journal of chemical information and modeling · 2026Article
- Mechanistic Insights into G Protein-Biased κ-Opioid Receptor Signaling Using Dual-Charged Naltrexamine Amides.Journal of medicinal chemistry · 2026Article
- Structure-based design of an opioid receptor modulator for enhanced morphine analgesia.Science advances · 2026Article
- Review
- An engineered nanobody inhibitor for molecular-to-circuit control of opioid receptor function.bioRxiv : the preprint server for biology · 2026Article
- Structural Basis of GPCR-Biased Modulation.Handbook of experimental pharmacology · 2026Review
- Differential Effects of Sodium on Agonist-Induced Conformational Transitions and Signaling at μ and κ Opioid Receptors.Biochemistry · 2025Article
- Nalfurafine is Aversive at Antinociceptive Doses in Mice.Pharmacology research & perspectives · 2025Article
- Structural and dynamic insights into the biased signaling mechanism of the human kappa opioid receptor.Nature communications · 2025Article
- Structural and dynamic studies uncover a distinct allosteric modulatory site at the μ-opioid receptor.bioRxiv : the preprint server for biology · 2025Article
- κ-Opioid Receptor Agonists as Robust Pain-Modulating Agents: Mechanisms and Therapeutic Potential in Pain Modulation.Journal of clinical medicine · 2025Review
- Differential effects of sodium on agonist-induced conformational transitions and signaling at μ and κ opioid receptors.bioRxiv : the preprint server for biology · 2025Article
- Synthesis and Pharmacology of a Morphinan-Derived Dual Mu-Kappa Opioid Receptor Agonist Analgesic.ACS chemical neuroscience · 2025Article
- Mechanistic insights from the atomic-level quaternary structure of short-lived GPCR oligomers of the human secretin receptor in live cells.Communications biology · 2025Article
- Anti-inflammatory and renoprotective effects of difelikefalin, a kappa opioid receptor agonist, in a rat model of renal ischemia-reperfusion-induced acute kidney injury.BMC nephrology · 2025Article
- Docking 14 Million Virtual Isoquinuclidines against the μ and κ Opioid Receptors Reveals Dual Antagonists-Inverse Agonists with Reduced Withdrawal Effects.ACS central science · 2025Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 4 countries.
Funding
Abstract
The κ-opioid receptor (KOR) has emerged as an attractive drug target for pain management without addiction, and biased signaling through particular pathways of KOR may be key to maintaining this benefit while minimizing side-effect liabilities. As for most G protein-coupled receptors (GPCRs), however, the molecular mechanisms of ligand-specific signaling at KOR have remained unclear. To better understand the molecular determinants of KOR signaling bias, we apply structure determination, atomic-level molecular dynamics (MD) simulations, and functional assays. We determine a crystal structure of KOR bound to the G protein-biased agonist nalfurafine, the first approved KOR-targeting drug. We also identify an arrestin-biased KOR agonist, WMS-X600. Using MD simulations of KOR bound to nalfurafine, WMS-X600, and a balanced agonist U50,488, we identify three active-state receptor conformations, including one that appears to favor arrestin signaling over G protein signaling and another that appears to favor G protein signaling over arrestin signaling. These results, combined with mutagenesis validation, provide a molecular explanation of how agonists achieve biased signaling at KOR.
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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.