ArticleNature chemical biology2023
Insights into distinct signaling profiles of the µOR activated by diverse agonists.
Article in Nature chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.
- Impact of adverse childhood experiences on analgesia-related outcomes: a systematic review.British journal of anaesthesia · 2025Pooled it
- Assessment of Abuse Potential-Related Effects of Oral Dried Kratom Leaf Powder in Healthy Normal Participants Following Single and Multiple Daily Doses.Drug testing and analysis · 2026Trial
- Structural basis of opioid receptor activation by PCP and ketamine.Nature structural & molecular biology · 2026Article
- Mechanisms and Manifestations of Ligand Bias in Signaling: Focus on Receptor Tyrosine Kinases.Chemical reviews · 2026Review
- Mechanistic insight into signal bias by the agonist-dependent conformational dynamics of GPR84.Nature communications · 2026Article
- Structural and dynamic studies uncover a distinct allosteric modulatory site at the µ-opioid receptor.Nature communications · 2026Article
- Atypical respiration patterns of kratom alkaloids.The Journal of pharmacology and experimental therapeutics · 2026Article
- Identification of Subtype-Selective Binding Sites in the Opioid Receptor Family.Journal of chemical information and modeling · 2026Article
- Mitragynine and Morphine Stabilize Different Conformations of the μ‑Opioid Receptor as Revealed by Molecular Dynamics Simulation Studies.ACS omega · 2026Article
- Investigating Opioid Receptor Activity through Biocatalytic Halogenation and Oxidation of Mitragynine.ACS chemical biology · 2026Article
- Slow Dissociation of Nitazenes from thebioRxiv : the preprint server for biology · 2026Article
- Article
- Indole Alkaloids as Biased Opioid Receptor Modulators.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Mechanistic Insights into G Protein-Biased κ-Opioid Receptor Signaling Using Dual-Charged Naltrexamine Amides.Journal of medicinal chemistry · 2026Article
- Discovery and dynamic pharmacology of μ-opioid receptor positive allosteric modulators.bioRxiv : the preprint server for biology · 2026Article
- Structure-based design of an opioid receptor modulator for enhanced morphine analgesia.Science advances · 2026Article
- Multifaceted modulation of human opioid receptors by kratom alkaloids: binding affinity, functional selectivity, and allosteric activity.Frontiers in pharmacology · 2026Article
- The molecular basis of μ-opioid receptor signaling plasticity.Cell research · 2025Article
- From kratom to 7-hydroxymitragynine: evolution of a natural remedy into a public-health threat.Pharmaceutical biology · 2025Review
- Structural and dynamic studies uncover a distinct allosteric modulatory site at the μ-opioid receptor.bioRxiv : the preprint server for biology · 2025Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 4 countries.
Funding
Abstract
Drugs targeting the μ-opioid receptor (μOR) are the most effective analgesics available but are also associated with fatal respiratory depression through a pathway that remains unclear. Here we investigated the mechanistic basis of action of lofentanil (LFT) and mitragynine pseudoindoxyl (MP), two μOR agonists with different safety profiles. LFT, one of the most lethal opioids, and MP, a kratom plant derivative with reduced respiratory depression in animal studies, exhibited markedly different efficacy profiles for G protein subtype activation and β-arrestin recruitment. Cryo-EM structures of μOR-Gi1 complex with MP (2.5 Å) and LFT (3.2 Å) revealed that the two ligands engage distinct subpockets, and molecular dynamics simulations showed additional differences in the binding site that promote distinct active-state conformations on the intracellular side of the receptor where G proteins and β-arrestins bind. These observations highlight how drugs engaging different parts of the μOR orthosteric pocket can lead to distinct signaling outcomes.
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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.