ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2019
Pharmacological effects of TAK-828F: an orally available RORγt inverse agonist, in mouse colitis model and human blood cells of inflammatory bowel disease.
Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 17 citations in OpenAlex.
- Circadian Rhythm Dysregulation in Inflammatory Bowel Disease: Mechanisms and Chronotherapeutic Approaches.International journal of molecular sciences · 2025Review
- Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases.Journal of pharmaceutical analysis · 2023Review
- Macrocyclic Retinoic Acid Receptor-Related Orphan Receptor C2 Inverse Agonists.ACS medicinal chemistry letters · 2023Article
- The role of group 3 innate lymphoid cell in intestinal disease.Frontiers in immunology · 2023Review
- Paradoxical Augmentation of Experimental Spondyloarthritis by RORC Inhibition in HLA-B27 Transgenic Rats.Frontiers in immunology · 2021Article
- Inhibition of the activation of γδT17 cells through PPARγ-PTEN/Akt/GSK3β/NFAT pathway contributes to the anti-colitis effect of madecassic acid.Cell death & disease · 2020Article
- Asymmetric Synthesis of a 5,6,7,8-Tetrahydro-1,6-naphthyridine Scaffold Leading to Potent Retinoid-Related Orphan Receptor γt Inverse Agonist TAK-828F.The Journal of organic chemistry · 2020Article
- VPR-254: an inhibitor of ROR-gamma T with potential utility for the treatment of inflammatory bowel disease.Inflammopharmacology · 2020Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
OBJECTIVE AND
designTo evaluate the potency of RORγt blockade for treatment of Inflammatory Bowel Disease (IBD), the efficacy of TAK-828F, a novel RORγt inverse agonist, in anti-TNF-α mAb non-responsive mouse colitis model and effect of TAK-828F on IL-17 production in peripheral mononuclear blood cells (PBMCs) of anti-TNF-α naive and treatment-failure patients of IBD was investigated. METHODS AND
resultsThe colitis model showed Th17-dependent pathogenicity and response to anti-IL-12/23p40 monoclonal antibody (mAb), but no response to anti-TNF-α mAb. In the model, TAK-828F, at oral dosages of 1 and 3 mg/kg, inhibited progression of colitis and reduced the immune reaction that characterize Th17 cells. Anti-IL-17A mAb showed neither efficacy nor change in the T cell population and colonic gene expression in the model. In the normal mouse, a 4-week treatment of TAK-828F at 30 mg/kg did not severely reduce lymphocyte cell counts in peripheral and intestinal mucosa, which was observed in RORγ
conclusionsThese results indicate that RORγt blockade would provide an effective approach for treating refractory patients with IBD by blocking IL-23/Th17 pathway.
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