ArticleCell2023
Structure-based discovery of conformationally selective inhibitors of the serotonin transporter.
Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
65 citing papers in PubMed, 2 syntheses or guidelines pooled it, 89 citations in OpenAlex.
- Japanese Cohort Study Identifies an Association Between the Serotonin Transporter-Linked Polymorphic Region and Suicide Death.Neuropsychopharmacology reports · 2026Pooled it
- Japanese Cohort Study and Meta-Analysis Demonstrate Significant Association Between Serotonin Transporter-Linked Polymorphic Region and Schizophrenia.Neuropsychopharmacology reports · 2026Pooled it
- Article
- Docking-based virtual screening: Past, present, and future.Biophysical journal · 2026Review
- Tryptophan metabolism in colorectal cancer: From mechanistic insights to novel therapeutic strategies.Clinical and translational medicine · 2026Review
- Solute carrier membrane transporters: emerging targets in CNS disorders.Nature reviews. Drug discovery · 2026Review
- Identification of novel serotonin transporter (SERT) inhibitors via large-scale machine learning-based virtual screening and molecular dynamics simulations.Molecular diversity · 2026Article
- Chemical Distance-Based Acceleration of Large Library Docking with ChemSTEP.ACS central science · 2026Article
- De novo design of miniproteins targeting GPCRs.Nature · 2026Article
- Modeling the Sensitivity of Large-Scale Virtual Screening to Scoring Function Accuracy, Artifacts, and Library Composition.Journal of chemical information and modeling · 2026Article
- Prioritizing neuroactive ligands using motif-guided virtual discovery and zebrafish profiling.npj drug discovery · 2026Article
- Technology-enabled insights into SLC transporters in MAFLD: redefining the multi-hit pathogenesis and therapeutic landscape.Acta pharmacologica Sinica · 2026Review
- The Selectivity Implications of Docking Libraries with Greater and Lesser Similarities to Bio-like Molecules.Journal of medicinal chemistry · 2026Article
- Beyond neurotransmission: the roles of serotonylation in physiological and pathological processes.Cellular & molecular biology letters · 2026Review
- Large Library Docking for Polypharmacology.Journal of medicinal chemistry · 2026Article
- Article
- The selectivity implications of docking libraries with greater and lesser similarities to bio-like molecules.bioRxiv : the preprint server for biology · 2026Article
- Structural basis for selective inhibition of human GABA transporter GAT3.Nature communications · 2026Article
- Prioritizing Neuroactive Ligands Using Motif-Guided Virtual Discovery and Zebrafish Profiling.bioRxiv : the preprint server for biology · 2026Article
- Deciphering Ibogaine's Matrix Pharmacology: Multiple Transporter Modulation at Serotonin Synapses.Journal of the American Chemical Society · 2026Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 2 countries.
Funding
Abstract
The serotonin transporter (SERT) removes synaptic serotonin and is the target of anti-depressant drugs. SERT adopts three conformations: outward-open, occluded, and inward-open. All known inhibitors target the outward-open state except ibogaine, which has unusual anti-depressant and substance-withdrawal effects, and stabilizes the inward-open conformation. Unfortunately, ibogaine's promiscuity and cardiotoxicity limit the understanding of inward-open state ligands. We docked over 200 million small molecules against the inward-open state of the SERT. Thirty-six top-ranking compounds were synthesized, and thirteen inhibited; further structure-based optimization led to the selection of two potent (low nanomolar) inhibitors. These stabilized an outward-closed state of the SERT with little activity against common off-targets. A cryo-EM structure of one of these bound to the SERT confirmed the predicted geometry. In mouse behavioral assays, both compounds had anxiolytic- and anti-depressant-like activity, with potencies up to 200-fold better than fluoxetine (Prozac), and one substantially reversed morphine withdrawal effects.
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What OpenQuestion holds
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.