ArticleNature structural & molecular biology2017
Crystal structures of human glycine receptor α3 bound to a novel class of analgesic potentiators.
Article in Nature structural & molecular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
What it found
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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
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.
- Cys-loop receptors on cannabinoids: All high?Frontiers in physiology · 2022Pooled it
- Breaking symmetry: Homomeric glycine receptor joins the asymmetric gating club.Structure (London, England : 1993) · 2026Article
- Structure of a pH-sensitive pentameric ligand-gated ion channel from the Sarcoptes scabies mite.Nature communications · 2026Article
- Structural basis for domain coupling in heteromeric glycine receptors revealed by an atypical allosteric agonist.Science advances · 2026Article
- Molecular determinants of cesium- and glycine-dependent glycine receptor activation.Scientific reports · 2025Article
- Φ value analysis underscores strong functional and structural compactness of the GABAProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Allosteric modulation and direct activation of glycine receptors by a tricyclic sulfonamide.Scientific reports · 2025Article
- Mechanisms underlying modulation of human GlyRα3 by ZnScience advances · 2024Article
- A millisecond coarse-grained simulation approach to decipher allosteric cannabinoid binding at the glycine receptor α1.Nature communications · 2024Article
- Gating mechanism of the human α1β GlyR by glycine.Structure (London, England : 1993) · 2024Article
- Exploring the Activation Process of the Glycine Receptor.Journal of the American Chemical Society · 2024Article
- Structural insights into the molecular effects of the anthelmintics monepantel and betaine on the Caenorhabditis elegans acetylcholine receptor ACR-23.The EMBO journal · 2024Article
- Structural insights into the allosteric inhibition of P2X4 receptors.Nature communications · 2023Article
- Asymmetric gating of a human hetero-pentameric glycine receptor.Nature communications · 2023Article
- An original potentiating mechanism revealed by the cryo-EM structures of the human α7 nicotinic receptor in complex with nanobodies.Nature communications · 2023Article
- Excitatory and inhibitory neuronal signaling in inflammatory and diabetic neuropathic pain.Molecular medicine (Cambridge, Mass.) · 2023Review
- Conformational transitions and allosteric modulation in a heteromeric glycine receptor.Nature communications · 2023Article
- Expression of Mutant Glycine Receptors inMembranes · 2022Article
- Lateral fenestrations in the extracellular domain of the glycine receptor contribute to the main chloride permeation pathway.Science advances · 2022Article
- Positive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies.Pharmacological reviews · 2022Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current therapies to treat persistent pain and neuropathic pain are limited by poor efficacy, side effects and risk of addiction. Here, we present a novel class of potent selective, central nervous system (CNS)-penetrant potentiators of glycine receptors (GlyRs), ligand-gated ion channels expressed in the CNS. AM-1488 increased the response to exogenous glycine in mouse spinal cord and significantly reversed mechanical allodynia induced by nerve injury in a mouse model of neuropathic pain. We obtained an X-ray crystal structure of human homopentameric GlyRα3 in complex with AM-3607, a potentiator of the same class with increased potency, and the agonist glycine, at 2.6-Å resolution. AM-3607 binds a novel allosteric site between subunits, which is adjacent to the orthosteric site where glycine binds. Our results provide new insights into the potentiation of cysteine-loop receptors by positive allosteric modulators and hold promise in structure-based design of GlyR modulators for the treatment of neuropathic pain.
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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.