ArticleJournal of medicinal chemistry2019
Development of an N-Acyl Amino Acid That Selectively Inhibits the Glycine Transporter 2 To Produce Analgesia in a Rat Model of Chronic Pain.
Article in Journal of medicinal chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- A Role for Glycine Transporter-2 Inhibitors in Regulating Accumbal Dopamine Levels and Voluntary Alcohol Intake in Rats.Alcohol, clinical & experimental research · 2026Article
- The PM20D1-OLE pathway induces microglia rewiring to ameliorate Alzheimer disease.Cell death & disease · 2026Article
- Transport and inhibition mechanisms of human glycine transporter 2.Nature communications · 2026Article
- A reversible allosteric inhibitor of GlyT2 for neuropathic pain without on-target side effects.Nature communications · 2026Article
- Mechanisms of transport and analgesic compounds recognition by glycine transporter 2.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A reversible allosteric inhibitor of GlyT2 alleviates neuropathic pain without on-target side effects.bioRxiv : the preprint server for biology · 2025Article
- Interactions Involving Glycine and Other Amino Acid Neurotransmitters: Focus on Transporter-Mediated Regulation of Release and Glycine-Glutamate Crosstalk.Biomedicines · 2024Review
- N-oleoyl alanine attenuates nicotine reward and spontaneous nicotine withdrawal in mice.Drug and alcohol dependence · 2024Article
- Membrane cholesterol regulates inhibition and substrate transport by the glycine transporter, GlyT2.Life science alliance · 2023Article
- Positive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies.Pharmacological reviews · 2022Review
- Analysis of Binding Determinants for Different Classes of Competitive and Noncompetitive Inhibitors of Glycine Transporters.International journal of molecular sciences · 2022Article
- Glycinergic Modulation of Pain in Behavioral Animal Models.Frontiers in pharmacology · 2022Review
- Inhibition of Glycine Re-Uptake: A Potential Approach for Treating Pain by Augmenting Glycine-Mediated Spinal Neurotransmission and Blunting Central Nociceptive Signaling.Biomolecules · 2021Review
- Pharmacological Evidence on Augmented Antiallodynia Following Systemic Co-Treatment with GlyT-1 and GlyT-2 Inhibitors in Rat Neuropathic Pain Model.International journal of molecular sciences · 2021Article
- MS Binding Assays for Glycine Transporter 2 (GlyT2) Employing Org25543 as Reporter Ligand.ChemMedChem · 2021Article
- Glycine Transporter 2: Mechanism and Allosteric Modulation.Frontiers in molecular biosciences · 2021Review
- A System for Assessing Dual Action Modulators of Glycine Transporters and Glycine Receptors.Biomolecules · 2020Article
- Advances in D-Amino Acids in Neurological Research.International journal of molecular sciences · 2020Review
- Allosteric Modulation of Neurotransmitter Transporters as a Therapeutic Strategy.Trends in pharmacological sciences · 2020Review
- Photoswitchable ORG25543 Congener Enables Optical Control of Glycine Transporter 2.ACS chemical neuroscience · 2020Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Inhibitors that target the glycine transporter 2, GlyT2, show promise as analgesics, but may be limited by their toxicity through complete or irreversible binding. Acyl-glycine inhibitors, however, are selective for GlyT2 and have been shown to provide analgesia in animal models of pain with minimal side effects, but are comparatively weak GlyT2 inhibitors. Here, we modify the simple acyl-glycine by synthesizing lipid analogues with a range of amino acid head groups in both l- and d-configurations, to produce nanomolar affinity, selective GlyT2 inhibitors. The potent inhibitor oleoyl-d-lysine (33) is also resistant to degradation in both human and rat plasma and liver microsomes, and is rapidly absorbed following an intraperitoneal injection to rats and readily crosses the blood-brain barrier. We demonstrate that 33 provides greater analgesia at lower doses, and does not possess the severe side effects of the very slowly reversible GlyT2 inhibitor, ORG25543 (2).
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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.