ArticleJournal of translational medicine2025
Discovery of therapeutic AGC2 modulators by combining docking, binding, and vesicle-based transport assays.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 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
4 citing papers in PubMed.
- Structural basis of ligand selectivity in FAD/NAD(P)H-dependent dehydrogenases: insights from trypanothione reductase and type II NADH dehydrogenase.Protein science : a publication of the Protein Society · 2026Article
- Suramin Interactions Across Biological Systems: From Molecular Targets to Therapeutic Implications.Biomolecules · 2026Review
- SLC25A mitochondrial carriers as biomarkers and therapeutic targets of spaceflight-induced dysfunction: the ADP/ATP carrier (AAC3) as a structural case study.Journal of translational medicine · 2025Article
- Correction: Discovery of therapeutic AGC2 modulators by combining docking, binding, and vesicle-based transport assays.Journal of translational medicine · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroudThe mitochondrial Aspartate/Glutamate Carrier 2 (AGC2), encoded by the SLC25A13 gene, plays a critical role in cellular metabolism and redox balance through the malate/aspartate shuttle. Dysregulation of AGC2 is implicated in rare genetic diseases and tumorigenesis, making it a promising therapeutic target.
methodsIn this study, we developed the first integrative platform for the discovery and validation of high-affinity AGC2 modulators, combining in silico screening with biophysical and functional assays. Docking-based virtual screening of chemical libraries was employed to identify candidate inhibitors. Their binding and inhibitory activity were validated via a combination of thermal shift assays and isothermal titration calorimetry (ITC) performed on n-dodecyl-β-D-maltoside (DDM)-based vesicles reconstituted with AGC2, alongside functional transport assays using AGC2-containing proteoliposomes.
resultsWe identified two previously unreported AGC2 inhibitors, suramin and taurolithocholic acid 3-sulfate. Remarkably, we report the first successful application of ITC to AGC2, overcoming major experimental challenges associated with ITC assays on the SLC25A family members, and achieving greater stability and reproducibility compared to similar assays performed on other family members, such as the ADP/ATP carrier and uncoupling proteins. Additionally, we present the first transmission electron microscopy (TEM) characterization of proteoliposomes and DDM-based vesicles reconstituted with AGC2, providing direct structural insights into the systems used for biophysical analysis.
conclusionsThis study establishes a reproducible, and scalable workflow that bridges high-throughput ligand identification with high-resolution kinetic characterization for targeting mitochondrial carriers.
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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.