ArticleScience advances2024
Identification of a targeted ACSL4 inhibitor to treat ferroptosis-related diseases.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 1 of them a synthesis that pooled it.
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Who cites it
109 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- Cuproptosis as a therapeutic target in cancer: a Systematic Review and bibliometric analysis of the research landscape.Frontiers in oncology · 2025Pooled it
- FTO-mediated mRNA biology · 2026Article
- Article
- Comorbid mechanisms of neuroinflammation and astrocytic ferroptosis in neurological disorders: A vicious cycle (Review).Biomedical reports · 2026Review
- Ferroptosis in liver biology and diseases.Hepatology communications · 2026Review
- Carrier-free nanoparticles in microneedles disrupt endosomal acidification suppress ferroptosis in radiation-induced oral mucositis.Materials today. Bio · 2026Article
- Ferroptosis in kidney disease.Nature reviews. Nephrology · 2026Review
- Exploring Ferroptosis: A Key Mechanism in Respiratory System Diseases and its Therapeutic Potential.Applied biochemistry and biotechnology · 2026Review
- The Substrate-Engine Model of Ferroptosis: Stage-Specific Targeting of Acyl-CoA Synthetase Long-Chain Family Member 4 and 5‑Lipoxygenase in Alzheimer's Disease.ACS pharmacology & translational science · 2026Review
- Multiple organ dysfunction syndrome: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Stiffness-tunable oral nanoparticles facilitate damaged islet β cell restoration for diabetes treatment.Science advances · 2026Article
- FerroScore: a statistical approach for quantifying tumor-related ferroptosis based on omics data.Briefings in bioinformatics · 2026Article
- Targeting Inflammation by Pioglitazone and its R-Enantiomer Mitigates Pathological Myocardial Remodeling in Murine Hypertrophic Cardiomyopathy.JACC. Basic to translational science · 2026Article
- A novel NAMPT activator ameliorates obesity by repressing ACSL1-dependent lipid synthesis.Acta pharmaceutica Sinica. B · 2026Article
- ACSL4 in Alzheimer's disease: Pathogenetic mechanisms and potential therapeutic targets.Genes & diseases · 2026Review
- Pathological mechanisms and therapeutic potential of MSC-Exos in ischemic stroke management.Stem cell research & therapy · 2026Review
- Dual targeting of NCF1 and NLRP3 by roburic acid orchestrates redox homeostasis and inhibits macrophage death in septic lung injury.Redox biology · 2026Article
- Roles of ACSL6 in lipid homeostasis and stress responses in the nervous system.Metabolic brain disease · 2026Review
- A therapeutic relay strategy enabled by spatiotemporally programmable nanoplatforms for multilayered cardioprotection against MI/RI.Journal of nanobiotechnology · 2026Article
- Monocyte-Derived Macrophage Ferroptosis Amplifies Cholangitis in Primary Biliary Cholangitis via a Calpain/ACSL4 Axis.Biomedicines · 2026Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ferroptosis is a form of iron-dependent, lipid peroxidation-driven regulatory cell death that has been implicated in the pathogenesis of multiple diseases, including organ injury, ischemia/reperfusion, and neurodegenerative diseases. However, inhibitors that directly and specifically target ferroptosis are not yet available. Here, we identify the compound AS-252424 (AS) as a potent ferroptosis inhibitor through kinase inhibitor library screening. Our results show that AS effectively inhibits lipid peroxidation and ferroptosis in both human and mouse cells. Mechanistically, AS directly binds to the glutamine 464 of ACSL4 to inhibit its enzymatic activity, resulting in the suppression of lipid peroxidation and ferroptosis. By using nanoparticle-based delivery systems, treatment with AS-loaded nanoparticles effectively alleviate ferroptosis-mediated organ injury in mouse models, including kidney ischemia/reperfusion injury and acute liver injury (ALI). Thus, our results identify that AS is a specific and targeted inhibitor of ACSL4 with remarkable antiferroptosis function, providing a potential therapeutic for ferroptosis-related diseases.
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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.