ArticleNature2016
Structure-based discovery of opioid analgesics with reduced side effects.
Open access · greenAbstract read
In one paragraph
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 504 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
504citing papers in PubMed, 3 pooled it
65.3field-weighted citation impact, top 1% of its field
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
504 citing papers in PubMed, 3 syntheses or guidelines pooled it, 930 citations in OpenAlex.
- Efficacy and safety of oliceridine versus sufentanil in perioperative anesthesia and analgesia: a systematic review and meta-analysis with trial sequential analysis.European journal of clinical pharmacology · 2026Pooled it
- Oliceridine versus sufentanil: a systematic review and meta-analysis of postoperative nausea and vomiting.BMC anesthesiology · 2026Pooled it
- The efficacy of parecoxib in improving pain after total knee or total hip arthroplasty: Systematic review and meta-analysis.Medicine · 2022Pooled it
- Effect of Oliceridine on the Acute Postoperative Pain Management After Elective Cesarean Delivery: A Randomized Non-Inferiority Trial.Drug design, development and therapy · 2026Trial
- Effective Dose of Oliceridine for Inhibiting Hemodynamic Elevation Induced by Tracheal Intubation: An Up-and-Down Sequential Trial.Drug design, development and therapy · 2025Trial
- Effective Dose of Oliceridine Fumarate Co-Administered with Remimazolam in Suppressing Gastroscope Insertion Responses for Adults.Drug design, development and therapy · 2025Trial
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- 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
- Internet Sales of "Research Grade Compounds": The Opioid SR-17018 (SR-17) as an Example.Cureus · 2026Review
- Structure-guided allosteric modulation of the delta opioid receptor.Nature communications · 2026Article
- Siteomix: a PyMOL plugin for the detection, alignment, and similarity analysis of protein‒ligand binding sites.Journal of computer-aided molecular design · 2026Article
- Mechanisms and Manifestations of Ligand Bias in Signaling: Focus on Receptor Tyrosine Kinases.Chemical reviews · 2026Review
- A Fentanyl-Responsive Microneedle Patch for Harm Reduction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Discovery of putative G-protein-biased µ-opioid agonists via hierarchical virtual screening of ultra-large chemical space.Molecular diversity · 2026Article
- Library Docking for Cannabinoid-2 Receptor Ligands.Journal of medicinal chemistry · 2026Article
- Discovery of a peripherally restricted αCell reports. Medicine · 2026Article
- Prioritizing neuroactive ligands using motif-guided virtual discovery and zebrafish profiling.npj drug discovery · 2026Article
- β-arrestin recruitment facilitates a direct association with G proteins.Nature communications · 2026Article
444 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 2 countries.
Aashish ManglikDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.
Henry LinDepartment of Pharmaceutical Chemistry, University of California, San Francisco, California 94158, USA.
Dipendra K AryalDepartment of Pharmacology, UNC Chapel Hill Medical School, Chapel Hill, North Carolina 27514, USA.
John D McCorvyDepartment of Pharmacology, UNC Chapel Hill Medical School, Chapel Hill, North Carolina 27514, USA.
Daniela DenglerDepartment of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schuhstraße 19, 91052 Erlangen, Germany.
Gregory CorderDepartment of Anesthesiology, Perioperative and Pain Medicine, Neurosurgery, Stanford Neurosciences Institute, Stanford University School of Medicine, Stanford, California 94305, USA.
Anat LevitDepartment of Pharmaceutical Chemistry, University of California, San Francisco, California 94158, USA.
Ralf C KlingDepartment of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schuhstraße 19, 91052 Erlangen, Germany.
Viachaslau BernatDepartment of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schuhstraße 19, 91052 Erlangen, Germany.
Harald HübnerDepartment of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schuhstraße 19, 91052 Erlangen, Germany.
Xi-Ping HuangDepartment of Pharmacology, UNC Chapel Hill Medical School, Chapel Hill, North Carolina 27514, USA.
Maria F SassanoDepartment of Pharmacology, UNC Chapel Hill Medical School, Chapel Hill, North Carolina 27514, USA.
Patrick M GiguèreDepartment of Pharmacology, UNC Chapel Hill Medical School, Chapel Hill, North Carolina 27514, USA.
Stefan LöberDepartment of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schuhstraße 19, 91052 Erlangen, Germany.
Da DuanDepartment of Pharmaceutical Chemistry, University of California, San Francisco, California 94158, USA.
Grégory ScherrerDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.
Brian K KobilkaDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.
Peter GmeinerDepartment of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schuhstraße 19, 91052 Erlangen, Germany.
Bryan L RothDepartment of Pharmacology, UNC Chapel Hill Medical School, Chapel Hill, North Carolina 27514, USA.
Brian K ShoichetDepartment of Pharmaceutical Chemistry, University of California, San Francisco, California 94158, USA.
Friedrich-Alexander-Universität Erlangen-Nürnberg · DEUniversity of California, San Francisco · USUniversity of North Carolina at Chapel Hill · USStanford University · USUniversity of North Carolina Health Care · USNeurosciences Institute · US
Funding
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007365 · NIGMS · STANFORD UNIVERSITY · PI CHUA, KATRIN F · 1985 to 2021
$33.8MMolecular Biophysics Training Program at StanfordT32GM008294 · NIGMS · STANFORD UNIVERSITY · PI HUANG, KERWYN C. · 1989 to 2019
$7.4MStructure-Function of Opioid ReceptorsP01DA035764 · NIDA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHEREZOV, VADIM, ROTH, BRYAN L. · 2014 to 2018
$7.1MBMI Bioinformatics Training GrantsT32GM067547 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HERNANDEZ, RYAN D. · 2003 to 2022
$6.6MStructure-based discovery of allosteric ligands for G Protein Coupled ReceptorsU19GM106990 · NIGMS · STANFORD UNIVERSITY · PI KOBILKA, BRIAN K · 2013 to 2017
$6.3MDESIGN AND EXPERIMENTAL TESTING OF NEW DOCKING METHODSR01GM059957 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SHOICHET, BRIAN K · 1999 to 2017
$4.4MStructural Basis of Opioid Receptor FunctionR37DA036246 · NIDA · STANFORD UNIVERSITY · PI KOBILKA, BRIAN K · 2013 to 2020
$4.2MDiterpines as Selective Kappa Opioid Receptor AgonistsR01DA017204 · NIDA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ROTH, BRYAN L. · 2003 to 2014
$3.2MThe structural basis for pathway-selective signaling by the µ opioid receptorR01DA036246 · NIDA · STANFORD UNIVERSITY · PI Brian K Kobilka · 2024 to 2026
$1.6MScalable technologies for illuminating the druggable GPCR-omeU01MH104974 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ROTH, BRYAN L., SHOICHET, BRIAN K · 2014 to 2016
$1.4MNIDA NIH HHS P01 DA035764NIDA NIH HHS R01 DA017204NIDA NIH HHS R01 DA036246NIDA NIH HHS R37 DA036246NIGMS NIH HHS R01 GM059957NIGMS NIH HHS T32 GM007365NIGMS NIH HHS T32 GM008294NIGMS NIH HHS T32 GM067547NIGMS NIH HHS U19 GM106990NIMH NIH HHS U01 MH104974
Abstract
Morphine is an alkaloid from the opium poppy used to treat pain. The potentially lethal side effects of morphine and related opioids-which include fatal respiratory depression-are thought to be mediated by μ-opioid-receptor (μOR) signalling through the β-arrestin pathway or by actions at other receptors. Conversely, G-protein μOR signalling is thought to confer analgesia. Here we computationally dock over 3 million molecules against the μOR structure and identify new scaffolds unrelated to known opioids. Structure-based optimization yields PZM21-a potent G
Indexed as
Drug DiscoveryAnalgesiaAnalgesics, OpioidAnimalsGTP-Binding Protein alpha Subunits, Gi-GoHEK293 CellsHumansMaleMiceMice, Inbred C57BLMice, KnockoutMolecular Docking SimulationPainReceptors, Opioid, muSpiro CompoundsStructure-Activity Relationship((3-methoxythiophen-2-yl)methyl)((2-(9-(pyridin-2-yl)-6-oxaspiro(4.5)decan-9-yl)ethyl))amineAnalgesics, OpioidGTP-Binding Protein alpha Subunits, Gi-GoPZM21 compoundReceptors, Opioid, muSpiro CompoundsThiophenesUrea
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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.