ArticleThe Journal of biological chemistry2013
Chemotype-selective modes of action of κ-opioid receptor agonists.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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
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Who cites it
36 citing papers in PubMed, 69 citations in OpenAlex.
- Identification of Subtype-Selective Binding Sites in the Opioid Receptor Family.Journal of chemical information and modeling · 2026Article
- κ-Opioid Receptor Agonists as Robust Pain-Modulating Agents: Mechanisms and Therapeutic Potential in Pain Modulation.Journal of clinical medicine · 2025Review
- Anticonvulsant Profiles of Three Hemorphin-4 Analogs with Rhodamine B in Mice.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Xylazine as an emerging new psychoactive substance; focuses on both 5-HTArchiv der Pharmazie · 2025Article
- Discovery of Novel, Selective, and Nonbasic Agonists for the Kappa-Opioid Receptor Determined by Salvinorin A-Based Virtual Screening.Journal of medicinal chemistry · 2024Article
- Review
- Additive Anticonvulsant Profile and Molecular Docking Analysis of 5,5'-Diphenylhydantoin Schiff Bases and Phenytoin.Biomedicines · 2023Article
- Cryo-EM structure of human κ-opioid receptor-Gi complex bound to an endogenous agonist dynorphin A.Protein & cell · 2023Article
- Article
- Solving an Old Puzzle: Elucidation and Evaluation of the Binding Mode of Salvinorin A at the Kappa Opioid Receptor.Molecules (Basel, Switzerland) · 2023Article
- Design of κ-Opioid Receptor Agonists for the Development of Potential Treatments of Pain with Reduced Side Effects.Molecules (Basel, Switzerland) · 2023Review
- In Vitro, In Vivo and In Silico Characterization of a Novel Kappa-Opioid Receptor Antagonist.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Mechanistic Characterization of the Pharmacological Profile of HS-731, a Peripherally Acting Opioid Analgesic, at the µ-, δ-, κ-Opioid and Nociceptin Receptors.Molecules (Basel, Switzerland) · 2022Article
- Structural Characterization of KOR Inactive and Active States for 3D Pharmacology and Drug Discovery.Handbook of experimental pharmacology · 2022Review
- Ketamine Metabolite (2ACS chemical neuroscience · 2021Article
- A Structure-Activity Relationship Comparison of Imidazodiazepines Binding at Kappa, Mu, and Delta Opioid Receptors and the GABAMolecules (Basel, Switzerland) · 2020Article
- Cutting-Edge Search for Safer Opioid Pain Relief: Retrospective Review of Salvinorin A and Its Analogs.Frontiers in psychiatry · 2019Review
- A review of salvinorin analogs and their kappa-opioid receptor activity.Bioorganic & medicinal chemistry letters · 2018Review
- Identifying Functional Hotspot Residues for Biased Ligand Design in G-Protein-Coupled Receptors.Molecular pharmacology · 2018Article
- Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
The crystal structures of opioid receptors provide a novel platform for inquiry into opioid receptor function. The molecular determinants for activation of the κ-opioid receptor (KOR) were studied using a combination of agonist docking, functional assays, and site-directed mutagenesis. Eighteen positions in the putative agonist binding site of KOR were selected and evaluated for their effects on receptor binding and activation by ligands representing four distinct chemotypes: the peptide dynorphin A(1-17), the arylacetamide U-69593, and the non-charged ligands salvinorin A and the octahydroisoquinolinone carboxamide 1xx. Minimally biased docking of the tested ligands into the antagonist-bound KOR structure generated distinct binding modes, which were then evaluated biochemically and pharmacologically. Our analysis identified two types of mutations: those that affect receptor function primarily via ligand binding and those that primarily affect function. The shared and differential mechanisms of agonist binding and activation in KOR are further discussed. Usually, mutations affecting function more than binding were located at the periphery of the binding site and did not interact strongly with the various ligands. Analysis of the crystal structure along with the present results provide fundamental insights into the activation mechanism of the KOR and suggest that "functional" residues, along with water molecules detected in the crystal structure, may be directly involved in transduction of the agonist binding event into structural changes at the conserved rotamer switches, thus leading to receptor activation.
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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.