ArticleCell death & disease2021
A small molecule binding HMGB1 inhibits caspase-11-mediated lethality in sepsis.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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
12 citing papers in PubMed, 19 citations in OpenAlex.
- Lipopolysaccharide and HMGB1: key regulatory factors in the pathophysiology of sepsis a mechanistic and therapeutic review.Frontiers in immunology · 2026Review
- New insights into the noncanonical inflammasome point to caspase-4 as a druggable target.Nature reviews. Immunology · 2025Review
- Preventive effect of small molecule active substances on septic cardiomyopathy after abdominal trauma: a systematic review and meta-analysis.Frontiers in pharmacology · 2025Article
- Role of Lipopolysaccharides in the Inflammation and Pyroptosis of Alveolar Epithelial Cells in Acute Lung Injury and Acute Respiratory Distress Syndrome.Journal of inflammation research · 2024Review
- Effector memory T cells induce innate inflammation by triggering DNA damage and a non-canonical STING pathway in dendritic cells.Cell reports · 2023Article
- In Situ Neutralization and Detoxification of LPS to Attenuate Hyperinflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- A prognostic assessment predicated by blood culture-based bacteria clustering from real-world evidence: Novel strategies and perspectives on prevention and management of sepsis.Frontiers in molecular biosciences · 2023Article
- Targeting HMGB1: A Potential Therapeutic Strategy for Chronic Kidney Disease.International journal of biological sciences · 2023Review
- HMGB1 is a critical molecule in the pathogenesis of Gram-negative sepsis.Journal of intensive medicine · 2022Review
- [Coactivator p300-induced H3K27 acetylation mediates lipopolysaccharide-induced inflammatory mediator synthesis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Modulation of the Gal-9/TIM-3 Immune Checkpoint with α-Lactose. Does Anomery of Lactose Matter?Cancers · 2021Review
- LPS-induced macrophage HMGB1-loaded extracellular vesicles trigger hepatocyte pyroptosis by activating the NLRP3 inflammasome.Cell death discovery · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Caspase-11, a cytosolic lipopolysaccharide (LPS) receptor, mediates lethal immune responses and coagulopathy in sepsis, a leading cause of death worldwide with limited therapeutic options. We previously showed that over-activation of caspase-11 is driven by hepatocyte-released high mobility group box 1 (HMGB1), which delivers extracellular LPS into the cytosol of host cells during sepsis. Using a phenotypic screening strategy with recombinant HMGB1 and peritoneal macrophages, we discovered that FeTPPS, a small molecule selectively inhibits HMGB1-mediated caspase-11 activation. The physical interaction between FeTPPS and HMGB1 disrupts the HMGB1-LPS binding and decreases the capacity of HMGB1 to induce lysosomal rupture, leading to the diminished cytosolic delivery of LPS. Treatment of FeTPPS significantly attenuates HMGB1- and caspase-11-mediated immune responses, organ damage, and lethality in endotoxemia and bacterial sepsis. These findings shed light on the development of HMGB1-targeting therapeutics for lethal immune disorders and might open a new avenue to treat sepsis.
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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.