ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
A Novel Drug Candidate for Sepsis Targeting Heparanase by Inhibiting Cytokine Storm.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. 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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Who cites it
12 citing papers in PubMed.
- Heparanase, Endothelial Dysfunction, and Cardiovascular Risk: The Emerging Role of Vitamin D.ACS pharmacology & translational science · 2026Review
- Artificial exosomes synergistically reshape sepsis immune homeostasis by modulating neutrophil fate and blocking PD-1/PD-L1.Cell reports. Medicine · 2026Article
- Diagnostic value of immune indicators and cytokines in sepsis after percutaneous nephrolithotomy (PCNL).Journal of medical biochemistry · 2026Article
- Endotheliopathy within the thromboinflammatory network of sepsis-induced coagulopathy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Targeting heparanase-associated epithelial glycocalyx remodeling attenuates Akt/NF-κB-related barrier dysfunction in experimental COPD.Frontiers in pharmacology · 2026Article
- Glycocalyx disruption mediates HP-PRRSV-induced microvascular endothelial dysfunction and underlies astragalus polysaccharide's antiviral efficacy.Open veterinary journal · 2026Article
- Unfractionated Heparin Attenuates Histone-Induced Pulmonary Endothelial Glycocalyx Injury: A Preliminary Study on the Roles of the ROCK Pathway and Heparanase‑1.Journal of inflammation research · 2026Article
- Glial Cells as Central Players in Neuroinflammation and Neuronal Damage Caused by Bacterial Pneumonia.Neuroimmunomodulation · 2026Review
- Intestine-Decipher Engineered Capsules Protect Against Sepsis-induced Intestinal Injury via Broad-spectrum Anti-inflammation and Parthanatos Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Vitamin C for sepsis: from mechanisms to individualized therapy.Frontiers in medicine · 2025Review
- The Preventive and Therapeutic Effects of Acute and Severe Inflammatory Disorders with Heparin and Heparinoid.Biomolecules · 2024Review
- A Novel Drug Candidate for Sepsis Targeting Heparanase by Inhibiting Cytokine Storm.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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Authors and funding
18 authors.
Funding
Abstract
Sepsis is an infection-triggered, rapidly progressive systemic inflammatory syndrome with a high mortality rate. Currently, there are no promising therapeutic strategies for managing this disease in the clinic. Heparanase plays a crucial role in the pathology of sepsis, and its inhibition can significantly relieve related symptoms. Here, a novel heparanase inhibitor CV122 is rationally designed and synthesized, and its therapeutic potential for sepsis with Lipopolysaccharide (LPS) and Cecal Ligation and Puncture (CLP)-induced sepsis mouse models are evaluated. It is found that CV122 potently inhibits heparanase activity in vitro, protects cell surface glycocalyx structure, and reduces the expression of adhesion molecules. In vivo, CV122 significantly reduces the systemic levels of proinflammatory cytokines, prevents organ damage, improves vitality, and efficiently protects mice from sepsis-induced death. Mechanistically, CV122 inhibits the activity of heparanase, reduces its expression in the lungs, and protects glycocalyx structure of lung tissue. It is also found that CV122 provides effective protection from organ damage and death caused by Crimean-Congo hemorrhagic fever virus (CCHFV) infection. These results suggest that CV122 is a potential drug candidate for sepsis therapy targeting heparanase by inhibiting cytokine storm.
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