ArticleEMBO reports2019
Diflunisal targets the HMGB1/CXCL12 heterocomplex and blocks immune cell recruitment.
Article in EMBO reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed.
- Damage-Associated Molecular Patterns in Mesothelioma: Drivers of Inflammation and Therapeutic Targets.International journal of molecular sciences · 2026Review
- Engineered HMGB1 construct with tandem Box B domains promotes tissue regeneration without potential for inflammation.iScience · 2026Article
- High Mobility Group Protein B1 Promotes Interferon Regulatory Factor 1 SUMOylation to Prime Trained Immunity of Circulating Monocytes and Aggravate the Progressive Synovial Inflammation in Knee Osteoarthritis.Research (Washington, D.C.) · 2026Article
- Anti-DAMP therapies for acute inflammation.Frontiers in immunology · 2025Review
- A potent nonapeptide inhibitor for the CXCL12/HMGB1 heterocomplex: A computational and experimental approach.Computational and structural biotechnology journal · 2025Article
- Effect of Diflunisal in Patients with Transthyretin Cardiomyopathy: A Pilot Study.Journal of clinical medicine · 2024Article
- Prognostic and therapeutic potential of senescent stromal fibroblasts in prostate cancer.Nature reviews. Urology · 2024Review
- The acidic intrinsically disordered region of the inflammatory mediator HMGB1 mediates fuzzy interactions with CXCL12.Nature communications · 2024Article
- Comparison of Pulmonary and Extrapulmonary Models of Sepsis-Associated Acute Lung Injury.Physiological research · 2023Article
- Chemokine Heteromers and Their Impact on Cellular Function-A Conceptual Framework.International journal of molecular sciences · 2023Review
- CXCL12/CXCR4 Axis is Involved in the Recruitment of NK Cells by HMGB1 Contributing to Persistent Airway Inflammation and AHR During the Late Stage of RSV Infection.Journal of microbiology (Seoul, Korea) · 2023Article
- The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention.Cellular & molecular immunology · 2023Review
- Upregulation of HMGB1 promotes vascular dysfunction in the soft palate of patients with obstructive sleep apnea via the TLR4/NF-κB/VEGF pathway.FEBS open bio · 2023Article
- Article
- HMGB1 is a Potential and Challenging Therapeutic Target for Parkinson's Disease.Cellular and molecular neurobiology · 2023Review
- The chemokine landscape: one system multiple shades.Frontiers in immunology · 2023Review
- Heterocomplexes between the atypical chemokine MIF and the CXC-motif chemokine CXCL4L1 regulate inflammation and thrombus formation.Cellular and molecular life sciences : CMLS · 2022Article
- Pamoic acid is an inhibitor of HMGB1·CXCL12 elicited chemotaxis and reduces inflammation in murine models of Pseudomonas aeruginosa pneumonia.Molecular medicine (Cambridge, Mass.) · 2022Article
- Molecular profiling of individual FDA-approved clinical drugs identifies modulators of nonsense-mediated mRNA decay.Molecular therapy. Nucleic acids · 2022Article
- High Mobility Group Box 1: Biological Functions and Relevance in Oxidative Stress Related Chronic Diseases.Cells · 2022Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Extracellular HMGB1 triggers inflammation following infection or injury and supports tumorigenesis in inflammation-related malignancies. HMGB1 has several redox states: reduced HMGB1 recruits inflammatory cells to injured tissues forming a heterocomplex with CXCL12 and signaling via its receptor CXCR4; disulfide-containing HMGB1 binds to TLR4 and promotes inflammatory responses. Here we show that diflunisal, an aspirin-like nonsteroidal anti-inflammatory drug (NSAID) that has been in clinical use for decades, specifically inhibits in vitro and in vivo the chemotactic activity of HMGB1 at nanomolar concentrations, at least in part by binding directly to both HMGB1 and CXCL12 and disrupting their heterocomplex. Importantly, diflunisal does not inhibit TLR4-dependent responses. Our findings clarify the mode of action of diflunisal and open the way to the rational design of functionally specific anti-inflammatory drugs.
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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.