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Pharmacological effects of TAK-828F: an orally available RORγt inverse agonist, in mouse colitis model and human blood cells of inflammatory bowel disease by Keiko Igaki; Yoshiki Nakamura; Masayuki Tanaka; Shinta Mizuno; Yusuke Yoshimatsu; Yusaku Komoike; Keiko Uga; Akira Shibata; Hisashi Imaichi; Satou Takayuki; Yoshimasa Ishimura; Masashi Yamasaki; Takanori Kanai; Yasuhiro Tsukimi; Noboru Tsuchimori is a Medicine article available to read on EtoBox.

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## Objective and design: To 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 results: The 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 mice. tak-828f strongly inhibited il-17 gene expression with ic values from 21.4 to 34.4 nmol/l in pbmcs from anti-tnf mab naive and treatment-failure patients of ibd. ## Conclusions: Thes

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Author

Keiko Igaki; Yoshiki Nakamura; Masayuki Tanaka; Shinta Mizuno; Yusuke Yoshimatsu; Yusaku Komoike; Keiko Uga; Akira Shibata; Hisashi Imaichi; Satou Takayuki; Yoshimasa Ishimura; Masashi Yamasaki; Takanori Kanai; Yasuhiro Tsukimi; Noboru Tsuchimori

Publisher

SP Birkhäuser Verlag Basel; Springer-Verlag; Birkhauser Verlag; Springer Science and Business Media LLC (ISSN 1420-908X)

Published

2019

Language

EN

Field

Medicine (Life Sciences)