ArticleNeuropharmacology2013
Structure-based discovery of antagonists for GluN3-containing N-methyl-D-aspartate receptors.
Article in Neuropharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 53 citations in OpenAlex.
- N-Methyl-D-aspartate receptors: structure, signaling and roles in atherosclerosis.Journal of translational medicine · 2026Review
- UCM-A86 is a selective positive allosteric modulator of GluN1/GluN3 NMDA receptors.Molecular pharmacology · 2026Article
- Emerging Roles of GluN3B NMDA Receptor Subunit in the Central Nervous System.Neuroscience bulletin · 2026Review
- Discovery of selective GluN1/GluN3A NMDA receptor inhibitors using integrated AI and physics-based approaches.Acta pharmacologica Sinica · 2026Article
- AI-enhanced virtual screening approach to hit identification for GluN1/GluN3A NMDA receptor.Acta pharmacologica Sinica · 2026Article
- The GluN3-containing NMDA receptors.Channels (Austin, Tex.) · 2025Review
- UCM-A86 is a selective positive allosteric modulator of GluN1/GluN3 NMDA receptors.bioRxiv : the preprint server for biology · 2025Article
- Discovery of novel GluN1/GluN3A NMDA receptor inhibitors using a deep learning-based method.Acta pharmacologica Sinica · 2025Article
- Contrastive learning-based drug screening model for GluN1/GluN3A inhibitors.Acta pharmacologica Sinica · 2025Article
- Discrete interneuron subsets participate in GluN1/GluN3A excitatory glycine receptor (eGlyR)-mediated regulation of hippocampal network activity throughout development and evolution.Research square · 2025Article
- Discrete interneuron subsets participate in GluN1/GluN3A excitatory glycine receptor (eGlyR)-mediated regulation of hippocampal network activity throughout development and evolution.bioRxiv : the preprint server for biology · 2025Article
- Distinct Regulation of Early Trafficking of the NMDA Receptors by the Ligand-Binding Domains of the GluN1 and GluN2A Subunits.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Plasticity in the Functional Properties of NMDA Receptors Improves Network Stability during Severe Energy Stress.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Structural prediction of GluN3 NMDA receptors.Frontiers in physiology · 2024Article
- Selective Cell-Surface Expression of Triheteromeric NMDA Receptors.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Plasticity in the functional properties of NMDA receptors improves network stability during severe energy stress.bioRxiv : the preprint server for biology · 2023Article
- Activation of excitatory glycine NMDA receptors: At the mercy of a whimsical GluN1 subunit.The Journal of general physiology · 2023Article
- Allosteric modulation of GluN1/GluN3 NMDA receptors by GluN1-selective competitive antagonists.The Journal of general physiology · 2023Article
- Article
- Derivatives of (Journal of medicinal chemistry · 2022Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
NMDA receptors are ligand-gated ion channels that assemble into tetrameric receptor complexes composed of glycine-binding GluN1 and GluN3 subunits (GluN3A-B) and glutamate-binding GluN2 subunits (GluN2A-D). NMDA receptors can assemble as GluN1/N2 receptors and as GluN3-containing NMDA receptors, which are either glutamate/glycine-activated triheteromeric GluN1/N2/N3 receptors or glycine-activated diheteromeric GluN1/N3 receptors. The glycine-binding GluN1 and GluN3 subunits display strikingly different pharmacological selectivity profiles. However, the pharmacological characterization of GluN3-containing receptors has been hampered by the lack of methods and pharmacological tools to study GluN3 subunit pharmacology in isolation. Here, we have developed a method to study the pharmacology of GluN3 subunits in recombinant diheteromeric GluN1/N3 receptors by mutating the orthosteric ligand-binding pocket in GluN1. This method is suitable for performing compound screening and characterization of structure-activity relationship studies on GluN3 ligands. We have performed a virtual screen of the orthosteric binding site of GluN3A in the search for antagonists with selectivity for GluN3 subunits. In the subsequent pharmacological evaluation of 99 selected compounds, we identified 6-hydroxy-[1,2,5]oxadiazolo[3,4-b]pyrazin-5(4H)-one (TK80) a novel competitive antagonist with preference for the GluN3B subunit. Serendipitously, we also identified [2-hydroxy-5-((4-(pyridin-3-yl)thiazol-2-yl)amino]benzoic acid (TK13) and 4-(2,4-dichlorobenzoyl)-1H-pyrrole-2-carboxylic acid (TK30), two novel non-competitive GluN3 antagonists. These findings demonstrate that structural differences between the orthosteric binding site of GluN3 and GluN1 can be exploited to generate selective ligands.
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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.