ArticleNature chemical biology2017
In silico design of novel probes for the atypical opioid receptor MRGPRX2.
Article in Nature chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers, 1 of them a synthesis that pooled it.
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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
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.
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Who cites it
130 citing papers in PubMed, 1 synthesis or guideline pooled it, 281 citations in OpenAlex.
- Neurotransmitter and neuropeptide regulation of mast cell function: a systematic review.Journal of neuroinflammation · 2020Pooled it
- Effect of Intradermal Morphine on Histaminergic and Non-Histaminergic Itch: A Randomised, Single-Blinded, Human Study.Experimental dermatology · 2025Trial
- Tetrahydrocurcumin suppresses FcεRI- and MRGPRX2-mediated mast cell activation and attenuates peanut-induced anaphylaxis in an in vitro and in vivo study.Pharmacological reports : PR · 2026Article
- International Union of Basic and Clinical Pharmacology. CXXII. Applying an objective evaluation to the status of class A orphan G protein-coupled receptors.Pharmacological reviews · 2026Review
- Structural determinants of ligand response specificity in the mast cell activating GPCR, MRGPRX2.The Journal of biological chemistry · 2026Article
- Pharmacological proximities in the GPCR family discovered using contact-informed amino-acid and binding pocket similarities.bioRxiv : the preprint server for biology · 2026Article
- In silico discovery of nanobody binders to a G-protein coupled receptor using AlphaFold-Multimer.Nature communications · 2026Article
- MRGPRX2 as a novel therapeutic target in headache.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Direct protamine activation of human mast cells is MRGPRX2-dependent and is modulated by heparin.The Journal of pharmacology and experimental therapeutics · 2026Article
- High-affinity recombinant antibodies enable a sensitive MRGPRX2-specific ELISA for detecting allergic rhinitis and chronic spontaneous urticaria.Analytical and bioanalytical chemistry · 2026Article
- Opioids regulate the functional state of immune cells and reduce inflammatory cardiac injury: Role of opioid receptors, MRGPRX2, and TLR4.Journal of biomedical research · 2026Article
- In silico assessment of neuromuscular blocking agents and fluoroquinolones as ligands of the Mas-related G protein-coupled receptor X2.Pharmacological reports : PR · 2026Article
- Regulation of MRGPRX2-mediated mast cell function by competence-stimulating peptide 1 and pro-adrenomedullin peptide.Frontiers in immunology · 2026Article
- Modulation of Mast Cell Activation via MRGPRX2 by Natural Oat Extract.International journal of molecular sciences · 2025Article
- Protein Structural Model Selection Informed by Comparison of Predicted Ligand Binding Poses.Journal of chemical information and modeling · 2025Article
- Icatibant Acts as a Balanced Ligand of MRGPRX2 in Human Skin Mast Cells.Biomolecules · 2025Article
- Mutations ofThe journal of allergy and clinical immunology. Global · 2025Review
- Aberrant Activation of Mast Cells: Molecular Mechanisms and Targets for Intervention.Clinical reviews in allergy & immunology · 2025Review
- Butyrate Selectively Targets Super-Enhancers and Transcriptional Networks Associated with Human Mast Cell Function.European journal of immunology · 2025Article
- Structural Determinants of Buprenorphine Partial Agonism at the μ-Opioid Receptor.Journal of chemical information and modeling · 2025Article
70 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
The primate-exclusive MRGPRX2 G protein-coupled receptor (GPCR) has been suggested to modulate pain and itch. Despite putative peptide and small-molecule MRGPRX2 agonists, selective nanomolar-potency probes have not yet been reported. To identify a MRGPRX2 probe, we first screened 5,695 small molecules and found that many opioid compounds activated MRGPRX2, including (-)- and (+)-morphine, hydrocodone, sinomenine, dextromethorphan, and the prodynorphin-derived peptides dynorphin A, dynorphin B, and α- and β-neoendorphin. We used these to select for mutagenesis-validated homology models and docked almost 4 million small molecules. From this docking, we predicted ZINC-3573-a potent MRGPRX2-selective agonist, showing little activity against 315 other GPCRs and 97 representative kinases-along with an essentially inactive enantiomer. ZINC-3573 activates endogenous MRGPRX2 in a human mast cell line, inducing degranulation and calcium release. MRGPRX2 is a unique atypical opioid-like receptor important for modulating mast cell degranulation, which can now be specifically modulated with ZINC-3573.
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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.