ArticleScience (New York, N.Y.)2017
A nontoxic pain killer designed by modeling of pathological receptor conformations.
Article in Science (New York, N.Y.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 113 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
113 citing papers in PubMed, 224 citations in OpenAlex.
- A Wireless Wearable Platform for Intravenous Drug Self-Administration in Freely Behaving Rats.bioRxiv : the preprint server for biology · 2026Article
- Artificial intelligence and ultra-high performance computing methods and experiments for drug discovery: virtual screening, deep learning, molecular dynamics simulations, ADMET modelling, and experimental validation.Molecular biomedicine · 2026Review
- Development of pH-Sensitive β‑Adrenergic Receptor Antagonists.ACS pharmacology & translational science · 2026Article
- Whole-body vibration decreases pain and cartilage degeneration in male and female mice with osteoarthritis.Pain reports · 2026Article
- Mechanisms of Location Bias in G Protein-Coupled Receptors.Handbook of experimental pharmacology · 2026Review
- The role of gut microbiota in neuropathic pain: insights into immune mechanisms.The journal of headache and pain · 2025Review
- Emerging therapeutic approaches for treating abdominal pain.Journal of the Canadian Association of Gastroenterology · 2025Review
- Molecular dynamics simulations of proteins: an in-depth review of computational strategies, structural insights, and their role in medicinal chemistry and drug development.Biological cybernetics · 2025Review
- Investigating Endogenous Opioids Unravels the Mechanisms Behind Opioid-Induced Constipation, a Mathematical Modeling Approach.International journal of molecular sciences · 2025Article
- Article
- Pain Signaling by GPCRs and RTKs.Trends in pharmacological sciences · 2025Review
- Article
- Impact of Fluorine Pattern on Lipophilicity and Acid-Base Properties of 2-(Thiofluoroalkyl)pyridines: Insights from Experiments and Statistical Modeling.Journal of medicinal chemistry · 2025Article
- Biased Opioid Receptor Agonists: Balancing Analgesic Efficacy and Side-Effect Profiles.International journal of molecular sciences · 2025Review
- Discovery of Novel pH-Sensitive μ-Opioid Receptor Agonists as Potent Analgesics with Reduced Side Effects.ACS medicinal chemistry letters · 2025Article
- A pH-sensitive opioid does not exhibit analgesic tolerance in a mouse model of colonic inflammation.British journal of pharmacology · 2025Article
- Origami with small molecules: exploiting the C-F bond as a conformational tool.Beilstein journal of organic chemistry · 2025Review
- Effects of pH on opioid receptor activation and implications for drug design.Biophysical journal · 2024Review
- Functional consequences of spatial, temporal and ligand bias of G protein-coupled receptors.Nature reviews. Nephrology · 2024Review
- Low-Efficacy Mu Opioid Agonists as Candidate Analgesics: Effects of Novel C-9 Substituted Phenylmorphans on Pain-Depressed Behavior in Mice.The Journal of pharmacology and experimental therapeutics · 2024Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Erratum issued
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Indiscriminate activation of opioid receptors provides pain relief but also severe central and intestinal side effects. We hypothesized that exploiting pathological (rather than physiological) conformation dynamics of opioid receptor-ligand interactions might yield ligands without adverse actions. By computer simulations at low pH, a hallmark of injured tissue, we designed an agonist that, because of its low acid dissociation constant, selectively activates peripheral μ-opioid receptors at the source of pain generation. Unlike the conventional opioid fentanyl, this agonist showed pH-sensitive binding, heterotrimeric guanine nucleotide-binding protein (G protein) subunit dissociation by fluorescence resonance energy transfer, and adenosine 3',5'-monophosphate inhibition in vitro
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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.