ArticleEBioMedicine2017
Suppression of NFAT5-mediated Inflammation and Chronic Arthritis by Novel κB-binding Inhibitors.
Article in EBioMedicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Review
- Mitochondrial SLC6A6 supports taurine transport.Nature metabolism · 2026Article
- SLC6A6 imports taurine into mitochondria to sustain mitochondrial translation and tumour growth.Nature metabolism · 2026Article
- Agonist signaling drives neutrophil subpopulations to promote/inhibit colorectal cancer liver metastasis.Nature communications · 2025Article
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
- Adequate post-ischemic reperfusion of the mouse brain requires endothelial NFAT5.Acta neuropathologica communications · 2024Article
- Modulators of Alpha-2 Macroglobulin Upregulation by High Glucose in Glomerular Mesangial Cells.Biomolecules · 2024Article
- NFAT5 governs cellular plasticity-driven resistance to KRAS-targeted therapy in pancreatic cancer.The Journal of experimental medicine · 2024Article
- Article
- TonEBP/NFAT5 expression is associated with cisplatin resistance and migration in macrophage-induced A549 cells.BMC molecular and cell biology · 2024Article
- Serum amyloid A expression in liver promotes synovial macrophage activation and chronic arthritis via NFAT5.The Journal of clinical investigation · 2024Article
- NFAT5 Restricts Bovine Herpesvirus 1 Productive Infection in MDBK Cell Cultures.Microbiology spectrum · 2023Article
- NLRC3 expression in macrophage impairs glycolysis and host immune defense by modulating the NF-κB-NFAT5 complex during septic immunosuppression.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- MiR-192-5p Alleviated Fibrosis and Inflammatory Responses of Tendon Cells by Targeting NFAT5.Computational and mathematical methods in medicine · 2022Article
- NFAT5 Amplifies Antipathogen Responses by Enhancing Chromatin Accessibility, H3K27 Demethylation, and Transcription Factor Recruitment.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- NFAT5 Deficiency Alleviates Formalin-Induced Inflammatory Pain Through mTOR.International journal of molecular sciences · 2021Article
- Abnormal NFAT5 Physiology in Duchenne Muscular Dystrophy Fibroblasts as a Putative Explanation for the Permanent Fibrosis Formation in Duchenne Muscular Dystrophy.International journal of molecular sciences · 2020Article
- Potential Role of Gene Regulator NFAT5 in the Pathogenesis of Diabetes Mellitus.Journal of diabetes research · 2020Review
- Prediction of Targets of Curculigoside A in Osteoporosis and Rheumatoid Arthritis Using Network Pharmacology and Experimental Verification.Drug design, development and therapy · 2020Article
- Regulation of Inflammatory Functions of Macrophages and T Lymphocytes by NFAT5.Frontiers in immunology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nuclear factor of activated T cells 5 (NFAT5) has been implicated in the pathogenesis of various human diseases, including cancer and arthritis. However, therapeutic agents inhibiting NFAT5 activity are currently unavailable. To discover NFAT5 inhibitors, a library of >40,000 chemicals was screened for the suppression of nitric oxide, a direct target regulated by NFAT5 activity, through high-throughput screening. We validated the anti-NFAT5 activity of 198 primary hit compounds using an NFAT5-dependent reporter assay and identified the novel NFAT5 suppressor KRN2, 13-(2-fluoro)-benzylberberine, and its derivative KRN5. KRN2 inhibited NFAT5 upregulation in macrophages stimulated with lipopolysaccharide and repressed the formation of NF-κB p65-DNA complexes in the NFAT5 promoter region. Interestingly, KRN2 selectively suppressed the expression of pro-inflammatory genes, including Nos2 and Il6, without hampering high-salt-induced NFAT5 and its target gene expressions. Moreover, KRN2 and KRN5, the latter of which exhibits high oral bioavailability and metabolic stability, ameliorated experimentally induced arthritis in mice without serious adverse effects, decreasing pro-inflammatory cytokine production. Particularly, orally administered KRN5 was stronger in suppressing arthritis than methotrexate, a commonly used anti-rheumatic drug, displaying better potency and safety than its original compound, berberine. Therefore, KRN2 and KRN5 can be potential therapeutic agents in the treatment of chronic arthritis.
Indexed as
Identifiers
What OpenQuestion holds
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.