ArticleInternational journal of molecular sciences2022
CS12192, a Novel JAK3/JAK1/TBK1 Inhibitor, Synergistically Enhances the Anti-Inflammation Effect of Methotrexate in a Rat Model of Rheumatoid Arthritis.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 11 citations in OpenAlex.
- 3D-QSAR and free energy landscape analysis for predicting novel JAK3 inhibitors in rheumatoid arthritis therapy.Scientific reports · 2026Article
- High-throughput 3D phenotypic screening identifies repurposed MEK inhibitors as drivers of chondrogenesis for cartilage regeneration.Frontiers in bioengineering and biotechnology · 2026Article
- Bone marrow mesenchymal stem cell-derived exosomes improve pyroptosis and mitochondrial integrity through miR-515-5p-mediated TLR4/NLRP3/GSDMD axis in rheumatoid arthritis.Arthritis research & therapy · 2025Article
- The Type I Interferon Axis in Systemic Autoimmune Diseases: From Molecular Pathways to Targeted Therapy.Biomolecules · 2025Review
- Role of IFN-α in Rheumatoid Arthritis.Current rheumatology reports · 2024Review
- Mutant p53Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
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Abstract
Rheumatoid arthritis (RA) is a common disease worldwide and is treated commonly with methotrexate (MTX). CS12192 is a novel JAK3 inhibitor discovered by Chipscreen Biosciences for the treatment of autoimmune diseases. In the present study, we examined the therapeutic effect of CS12192 against RA and explored if the combinational therapy of CS12192 and MTX produced a synergistic effect against RA in rat collagen-induced arthritis (CIA). Arthritis was induced in male Sprague-Dawley rats by two intradermal injections of bovine type II collagen (CII) and treated with MTX, CS12192, or the combination of CS12192 and MTX daily for two weeks. Effects of different treatments on arthritis score, X-ray score, pathology, and expression of inflammatory cytokines and biomarkers were examined. We found that treatment with either CS12192 or MTX produced a comparable therapeutic effect on CIA including: (1) significantly lowering the arthritis score, X-ray score, serum levels of rheumatic factor (RF), C-reactive protein (CRP), and anti-nuclear antibodies (ANA); (2) largely alleviating histopathological damage, reducing infiltration of Th17 cells while promoting Treg cells; (3) inhibiting the expression of inflammatory cytokines and chemokines such as IL-1β, TNF-α, IL-6, CCL2, and CXCL1. All these inhibitory effects were further improved by the combinational therapy with MTX and CS12192. Of importance, the combinational treatment also resulted in a marked switching of the Th17 to Treg and the M1 to M2 immune responses in synovial tissues of CIA. Thus, when compared to the monotherapy, the combination treatment with CS12192 and MTX produces a better therapeutic effect against CIA with a greater suppressive effect on T cells and macrophage-mediated joint inflammation.
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