ArticleNature communications2025
Modulation of the human GlyT1 by clinical drugs and cholesterol.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 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
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
8 citing papers in PubMed.
- Unique fluoroalkyl substituents: is there life after CFChemical science · 2026Review
- GlyT1 (SLC6A9) inhibition in neurological and psychiatric disorders.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Structural basis for the transport mechanism and cholesterol modulation of the human proline transporter.Nature communications · 2026Article
- Structural mechanism of substrate binding and inhibition of human taurine transporter.Nature communications · 2026Article
- Modulation of glycine transporters as a novel therapeutic strategy in neuropsychiatry.Psychopharmacology · 2026Review
- 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
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- GlyT1 inhibition by ALX-5407 attenuates allograft rejection through suppression of Th1 cell differentiation.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycine transporter 1 (GlyT1) is a key player in shaping extracellular glutamatergic signaling processes and holds promise for treating cognitive impairments associated with schizophrenia by inhibiting its activity and thus enhancing the function of NMDA receptors. Despite its significant role in physiological and pharmacology, its modulation mechanism by clinical drugs and internal lipids remains elusive. Here, we determine cryo-EM structures of GlyT1 in its apo state and in complex with clinical trial drugs iclepertin and sarcosine. The GlyT1 in its apo state is determined in three distinct conformations, exhibiting a conformational equilibrium of the transport cycle. The complex structures with inhibitor iclepertin and sarcosine elucidate their unique binding poses with GlyT1. Three binding sites of cholesterol are determined in GlyT1, two of which are conformation-dependent. Transport kinetics studies reveal that a delicate binding equilibrium for cholesterol is crucial for the conformational transition of GlyT1. This study significantly enhances our understanding of the physiological and pharmacological aspects of GlyT1.
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