ArticleAnnals of the rheumatic diseases2019
Fexofenadine inhibits TNF signaling through targeting to cytosolic phospholipase A2 and is therapeutic against inflammatory arthritis.
Article in Annals of the rheumatic diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 55 citations in OpenAlex.
- Macrophage Lipid Homeostasis Drives IVDD via a Senescence-Dependent Impairment of Efferocytosis.Cell proliferation · 2026Article
- Menaquinone-7 alleviates mitochondrial dysfunction and senescence in senile osteoporosis by targeting the PINK1-mediated mitophagy via PXR/ERK/CREB signaling pathway.Journal of pharmaceutical analysis · 2026Article
- Dabigatran Attenuates Osteoporosis by Balancing Osteoblastogenesis and Osteoclastogenesis by Targeting PRKAB1 and RELA.Research (Washington, D.C.) · 2026Article
- NEO1 modulates the A1 astrocyte polarization in subarachnoid hemorrhage through the cPLA2-MAVS signaling pathway.Journal of neuroinflammation · 2025Article
- Fexofenadine protects against osteoarthritis by targeting Smad2 and STAT1 to enhance anabolism and binding cPLA2 to inhibit catabolism.Cell death discovery · 2025Article
- Cytosolic phospholipase A2 as a therapeutic target for degenerative joint diseases.Bone research · 2025Article
- Exogenous pyruvate is therapeutic against colitis by targeting cytosolic phospholipase A2.Genes & diseases · 2025Article
- cPLACytotechnology · 2025Article
- The Potential ofInternational journal of molecular sciences · 2025Article
- Arachidonic acid in aging: New roles for old players.Journal of advanced research · 2025Review
- Targeting TRPC channels for control of arthritis-induced bone erosion.Science advances · 2025Article
- Emodin mitigates rheumatoid arthritis through direct binding to TNF-α.Frontiers in pharmacology · 2025Article
- 10-hydroxy-2-decenoic acid prevents osteoarthritis by targeting aspartyl β hydroxylase and inhibiting chondrocyte senescence in male mice preclinically.Nature communications · 2024Article
- Fexofenadine As Successful Adjunctive Treatment of Rheumatoid Arthritis and Trochanteric Bursitis: A Case Report.Cureus · 2024Article
- Dietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice.Protein & cell · 2024Article
- Integration of National Health Insurance claims data and animal models reveals fexofenadine as a promising repurposed drug for Parkinson's disease.Journal of neuroinflammation · 2024Article
- Atsttrin regulates osteoblastogenesis and osteoclastogenesis through the TNFR pathway.Communications biology · 2023Article
- Article
- Ångstrom-scale silver particles ameliorate collagen-induced and K/BxN-transfer arthritis in mice via the suppression of inflammation and osteoclastogenesis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Tau deficiency inhibits classically activated macrophage polarization and protects against collagen-induced arthritis in mice.Arthritis research & therapy · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveTumour necrosis factor alpha (TNF-α) signalling plays a central role in the pathogenesis of various autoimmune diseases, particularly inflammatory arthritis. This study aimed to repurpose clinically approved drugs as potential inhibitors of TNF-α signalling in treatment of inflammatory arthritis.
methodsIn vitro and in vivo screening of an Food and Drug Administration (FDA)-approved drug library; in vitro and in vivo assays for examining the blockade of TNF actions by fexofenadine: assays for defining the anti-inflammatory activity of fexofenadine using TNF-α transgenic (TNF-tg) mice and collagen-induced arthritis in DBA/1 mice. Identification and characterisation of the binding of fexofenadine to cytosolic phospholipase A2 (cPLA2) using drug affinity responsive target stability assay, proteomics, cellular thermal shift assay, information field dynamics and molecular dynamics; various assays for examining fexofenadine inhibition of cPLA2 as well as the dependence of fexofenadine's anti-TNF activity on cPLA2.
resultsSerial screenings of a library composed of FDA-approved drugs led to the identification of fexofenadine as an inhibitor of TNF-α signalling. Fexofenadine potently inhibited TNF/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) signalling in vitro and in vivo, and ameliorated disease symptoms in inflammatory arthritis models. cPLA2 was isolated as a novel target of fexofenadine. Fexofenadine blocked TNF-stimulated cPLA2 activity and arachidonic acid production through binding to catalytic domain 2 of cPLA2 and inhibition of its phosphorylation on Ser-505. Further, deletion of cPLA2 abolished fexofenadine's anti-TNF activity.
conclusionCollectively, these findings not only provide new insights into the understanding of fexofenadine action and underlying mechanisms but also provide new therapeutic interventions for various TNF-α and cPLA2-associated pathologies and conditions, particularly inflammatory rheumatic diseases.
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.