ArticleScientific reports2023
Alleviation of arthritis through prevention of neutrophil extracellular traps by an orally available inhibitor of protein arginine deiminase 4.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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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
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Investigating the Role of Neutrophil Extracellular Traps as a Therapeutic Target in Traumatic Brain Injury: a Systematic Review and Meta-analysis.Molecular neurobiology · 2025Pooled it
- PAD4-DB: A Curated Structure-Activity Resource Reveals Hub-Organized Activity Cliffs and Scaffold-Dependent SAR Ruggedness in PAD4 Inhibitors.International journal of molecular sciences · 2026Article
- Cell death crosstalk in NET-Driven inflammation: mechanisms, disease contexts, and therapeutic perspectives.Biomarker research · 2026Review
- Insulin preservatives trigger neutrophil extracellular trap formation through SYNE1-mediated nuclear disassembly.bioRxiv : the preprint server for biology · 2026Article
- The Role of Neutrophil Extracellular Traps (NETs) in the Pathogenesis of Ovarian Cancer: New Insight and Future Perspectives.Molecular biotechnology · 2026Review
- Differential presence of neutrophil extracellular traps in serum vs plasma of patients with critical limb-threatening ischemia.Research and practice in thrombosis and haemostasis · 2026Article
- Targeting Neutrophil Function as Therapy for Hidradenitis Suppurativa.International journal of molecular sciences · 2026Review
- Sex differences in disease severity and immune responses in murine and human inflammatory arthritis.Biology of sex differences · 2026Article
- Neutrophil Extracellular Traps and Complement Pathways: The Missing Links in Acute Rheumatic Fever and Rheumatic Heart Disease Pathogenesis.Journal of cardiovascular translational research · 2026Review
- Mitochondria as Inducers of Neutrophil Extracellular Traps.Inflammation · 2026Review
- Interleukin-33 Promotes Neutrophil Extracellular Trap Formation To Aggravate Renal Ischemia-Reperfusion Injury Through ST2/PI3K/Akt and ST2/PAD4 Pathways.Inflammation · 2026Article
- Molecular basis of post-translational neoantigen generation in rheumatoid arthritis: breaking immunological tolerance and implications for targeted therapy.Frontiers in immunology · 2026Review
- Peptidylarginine deiminase 4-mediated citrullination in human disease: molecular mechanisms and therapeutic targeting.Frontiers in pharmacology · 2026Review
- Mapping benefit, risk, and opportunity in PAD4 inhibition.Frontiers in immunology · 2026Review
- Bimodal regulation and precision therapy of neutrophil extracellular traps in liver ischemia-reperfusion injury: recent advances.Frontiers in immunology · 2026Review
- Citrullination Accompanies the Development of Carotid Atherosclerotic Plaques.Current medicinal chemistry · 2026Article
- Periodontitis Leads to Systemic Bone Loss through Neutrophil Reprogramming.Journal of dental research · 2026Article
- Peptidylarginine Deiminases: An Overview of Recent Advances in Citrullination Research.International journal of molecular sciences · 2025Review
- Citrullination in Tumor Metastasis, Inside and Outside the Cells.Cancer science · 2025Review
- NETs in ovarian cancer progression: innovative nanoparticle-based therapeutic strategies.European journal of medical research · 2025Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Protein arginine deiminases (PAD) 4 is an enzyme that catalyzes citrullination of protein and its role in autoimmune diseases has been established through clinical genetics and gene knock out studies in mice. Further, studies with PAD4 - deficient mice have shown that PAD4 deficiency does not lead to increased infection or immune suppression, which makes PAD4 an attractive therapeutic target for auto-immune and inflammatory diseases. PAD4 has critical enzymatic role of promoting chromatin decondensation and neutrophil extracellular traps (NETs) formation that is associated with a number of immune-mediated pathological conditions. Here, we present a non-covalent PAD4 inhibitor JBI-589 with high PAD4 isoform selectivity and delineated its binding mode at 2.88 Å resolution by X-ray crystallography. We confirmed its effectiveness in inhibiting NET formation in vitro. Additionally, by using two mouse arthritis models for human rheumatoid arthritis (RA), the well-known disease associated with PAD4 clinically, we established its efficacy in vivo. These results suggest that JBI-589 would be beneficial for both PAD4 and NET-associated pathological conditions.
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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.