ArticleAngewandte Chemie (International ed. in English)2025
LIBX-A401: A Novel Selective Inhibitor of Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4) and Its Binding Mode.
Article in Angewandte Chemie (International ed. in English), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 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
5 citing papers in PubMed.
- ACSL4 Inhibition by AS-252424 Protects Visual Function by Suppressing RGC Ferroptosis After Retinal Ischemia Reperfusion Injury.Molecular neurobiology · 2026Article
- Bioengineering Strategies to Address Key Bottlenecks in Ferroptosis-Based Cancer Therapy: A Critical Review.International journal of nanomedicine · 2026Review
- State-of-the-Art and Future Directions in Structural Proteomics.Molecular & cellular proteomics : MCP · 2025Review
- LIBX-A401: A Novel Selective Inhibitor of Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4) and Its Binding Mode.Angewandte Chemie (International ed. in English) · 2025Article
- Ferroptosis in Hypertriglyceridemic Acute Pancreatitis: Mechanisms and Therapeutic Implications.Journal of inflammation research · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors.
Funding
Abstract
Acyl-coenzyme A synthetase long-chain family member 4 (ACSL4), a pivotal enzyme in lipid metabolism, has emerged as a therapeutic target for ferroptosis-related conditions and cancer. However, its reference inhibitor, rosiglitazone, has off-target activity on peroxisome proliferator-activated receptor gamma (PPARγ), a key regulator of lipid homeostasis. Here, the discovery of LIBX-A401, a potent ACSL4 inhibitor derived from rosiglitazone devoid of PPARγ activity, is reported. Its binding to ACSL4 is ATP-dependent, stabilizing the C-terminal domain and altering the fatty acid gate region, as shown by Hydrogen-Deuterium Exchange Mass Spectrometry. Photoaffinity labeling identified A329 within the fatty acid binding site, while molecular dynamics and mutagenesis highlighted Q302 as critical for LIBX-A401 binding. LIBX-A401 exhibits anti-ferroptotic properties in cells, supported by target engagement. These findings establish LIBX-A401 as a valuable tool to study ACSL4 in ferroptosis and cancer, while its elucidated binding mode paves the way for the rational design of improved inhibitors.
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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.