ArticleFrontiers in immunology2023
KW2449 ameliorates collagen-induced arthritis by inhibiting RIPK1-dependent necroptosis.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Gut microbiota dysbiosis and metabolic alterations in rheumatoid arthritis: a barrier to periodontal repair.RMD open · 2026Article
- The "Tianyu" Formulation Alleviates Rheumatoid Arthritis by Modulating the NLRP3/Caspase-1/GSDMD-Mediated Pyroptosis Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Molecular Dynamics-Guided Design and Chemoproteomic Profiling of Covalent Kinase Activity Probes.Journal of the American Chemical Society · 2026Article
- Frontier research on mechanisms of bone destruction in rheumatoid arthritis.Frontiers in cell and developmental biology · 2026Review
- Targeting pyroptosis in periodontitis: mechanisms and therapeutic strategies.Frontiers in immunology · 2026Review
- Molecular Dynamics-Guided Design and Chemoproteomic Profiling of Covalent Kinase Activity Probes.bioRxiv : the preprint server for biology · 2025Article
- Dysregulation of Different Modes of Programmed Cell Death in Rheumatoid Arthritis Fibroblast-Like Synoviocyte.International journal of rheumatic diseases · 2025Review
- KW-2449 Ameliorates Cardiac Dysfunction in a Rat Model of Sepsis-Induced Cardiomyopathy.Inflammation · 2025Article
- The Dual Role of TRADD in Liver Disease: From Cell Death Regulation to Inflammatory Microenvironment Remodeling.International journal of molecular sciences · 2025Review
- Programmed Cell Death in Rheumatoid Arthritis.Journal of inflammation research · 2025Review
- Significance of Necroptosis in Cartilage Degeneration.Biomolecules · 2024Review
- Adipose-derived stem cell exosomes loaded with icariin alleviates rheumatoid arthritis by modulating macrophage polarization in rats.Journal of nanobiotechnology · 2024Article
- E3 ubiquitin ligase geneFrontiers in immunology · 2024Review
- Association of RIPK1 and RIPK2 Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Han Population.The application of clinical genetics · 2024Article
- Repressive Control of Keratinocyte Cytoplasmic Inflammatory Signaling.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Objective: Necroptosis has recently been found to be associated with the pathogenesis of many autoimmune diseases, including rheumatoid arthritis (RA). This study was undertaken to explore the role of RIPK1-dependent necroptosis in the pathogenesis of RA and the potential new treatment options. Methods: The plasma levels of receptor-interacting protein kinase 1 (RIPK1) and mixed lineage kinase domain-like pseudokinase (MLKL) in 23 controls and 42 RA patients were detected by ELISA. Collagen-induced arthritis (CIA) rats were treated with KW2449 by gavage for 28 days. Arthritis index score, H&E staining, and Micro-CT analysis were used to evaluate joint inflammation. The levels of RIPK1-dependent necroptosis related proteins and inflammatory cytokines were detected by qRT-PCR, ELISA and Western blot, and the cell death morphology was detected by flow cytometry analysis and high-content imaging analysis. Results: The plasma levels of RIPK1 and MLKL in RA patients were higher than those in healthy people, and were positively correlated with the severity of RA. KW2449 could reduce joint swelling, joint bone destruction, tissue damage, and the plasma levels of inflammatory cytokines in CIA rats. Lipopolysaccharide combined with zVAD (LZ) could induce necroptosis in RAW 264.7 cells, which could be reduced by KW2449. RIPK1-dependent necroptosis related proteins and inflammatory factors increased after LZ induction and decreased after KW2449 treatment or knockdown of RIPK1. Conclusion: These findings suggest that the overexpression of RIPK1 is positively correlated with the severity of RA. KW2449, as a small molecule inhibitor targeting RIPK1, has the potential to be a therapeutic strategy for RA treatment by inhibiting RIPK1-dependent necroptosis.
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