ArticleJournal of medicinal chemistry2015
Ensemble-based virtual screening for cannabinoid-like potentiators of the human glycine receptor α1 for the treatment of pain.
Article in Journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Cys-loop receptors on cannabinoids: All high?Frontiers in physiology · 2022Pooled it
- Centralized Review of Alzheimer's Disease and Related Dementias Biomedical Repositories and Computational Methods.Bioengineering (Basel, Switzerland) · 2026Review
- Cannabidiol ameliorates cognitive decline in 5×FAD mouse model of Alzheimer's disease through potentiating the function of extrasynaptic glycine receptors.Molecular psychiatry · 2025Article
- Novel Scaffold Agonists of the αMolecules (Basel, Switzerland) · 2024Article
- Positive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies.Pharmacological reviews · 2022Review
- Combined alcohol and cannabinoid exposure leads to synergistic toxicity by affecting cerebellar Purkinje cells.Nature metabolism · 2022Article
- Structural basis for cannabinoid-induced potentiation of alpha1-glycine receptors in lipid nanodiscs.Nature communications · 2022Article
- Effects of cannabinoids on ligand-gated ion channels.Frontiers in physiology · 2022Review
- Drug repurposing against SARS-CoV-2 receptor binding domain using ensemble-based virtual screening and molecular dynamics simulations.Computers in biology and medicine · 2021Article
- Membrane cholesterol dependence of cannabinoid modulation of glycine receptor.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Modulation of Glycine Receptor-Mediated Pain SignalingFrontiers in molecular neuroscience · 2019Article
- Structural basis of neurosteroid anesthetic action on GABANature communications · 2018Article
- Glycine receptors and glycine transporters: targets for novel analgesics?Cellular and molecular life sciences : CMLS · 2018Review
- Structural Basis of Alcohol Inhibition of the Pentameric Ligand-Gated Ion Channel ELIC.Structure (London, England : 1993) · 2017Article
- Computational methods in drug discovery.Beilstein journal of organic chemistry · 2016Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The human glycine receptors (hGlyRs) are chloride-selective ion channels that mediate inhibitory neurotransmission in the brain stem and spinal cord. They are also targets for compounds of potential use in analgesic therapies. Here, we develop a strategy to discover analgesic drugs via structure-based virtual screening based on the recently published NMR structure of the hGlyR-α1 transmembrane domain (PDB ID: 2M6I ) and the critical role of residue S296 in hGlyR-α1 potentiation by Δ(9)-tetrahydrocannabinol (THC). We screened 1549 FDA-approved drugs in the DrugBank database on an ensemble of 180 hGlyR-α1 structures generated from molecular dynamics simulations of the NMR structure of the hGlyR-α1 transmembrane domain in different lipid environments. Thirteen hit compounds from the screening were selected for functional validation in Xenopus laevis oocytes expressing hGlyR-α1. Only one compound showed no potentiation effects; seven potentiated hGlyR-α1 at a level greater than THC at 1 μM. Our virtual screening protocol is generally applicable to drug targets with lipid-facing binding sites.
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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.