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Pharmaceuticals 2014, 7(1), 1-17; doi:10.3390/ph7010001
Article

A New Phenylpyrazoleanilide, Y-320, Inhibits Interleukin 17 Production and Ameliorates Collagen-Induced Arthritis in Mice and Cynomolgus Monkeys

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Received: 5 November 2013; in revised form: 16 December 2013 / Accepted: 18 December 2013 / Published: 23 December 2013
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Abstract: Interleukin (IL)-15 and IL-17 are thought to play an important role in the pathogenesis of rheumatoid arthritis (RA) because both pro-inflammatory cytokines are found in synovial fluid of RA patients. In this study, we examined the pharmacological profiles of Y-320, a new phenylpyrazoleanilide immunomodulator. Y-320 inhibited IL-17 production by CD4 T cells stimulated with IL-15 with IC50 values of 20 to 60 nM. Oral administration of Y-320 (0.3 to 3 mg/kg) significantly inhibited the development and progression of arthritis and joint destruction with reduction of IL-17 mRNA expression in arthritic joints of type II collagen-induced arthritis (CIA) in DBA/1J mice. Y-320 in combination with anti-murine tumor necrosis factor-α monoclonal antibody showed a synergistic effect on mouse CIA. Moreover, therapeutic treatment with Y-320 (0.3 and 1 mg/kg orally) ameliorated CIA in cynomolgus monkeys. Our results suggest that Y-320, an orally active inhibitor for IL-17 production, provides a useful therapy for RA.
Keywords: interleukin 15 (IL-15); interleukin 17 (IL-17); phenylpyrazoleanilide; Y-320; immunomodulator; collagen-induced arthritis (CIA); rheumatoid arthritis (RA) interleukin 15 (IL-15); interleukin 17 (IL-17); phenylpyrazoleanilide; Y-320; immunomodulator; collagen-induced arthritis (CIA); rheumatoid arthritis (RA)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Ushio, H.; Ishibuchi, S.; Oshita, K.; Seki, N.; Kataoka, H.; Sugahara, K.; Adachi, K.; Chiba, K. A New Phenylpyrazoleanilide, Y-320, Inhibits Interleukin 17 Production and Ameliorates Collagen-Induced Arthritis in Mice and Cynomolgus Monkeys. Pharmaceuticals 2014, 7, 1-17.

AMA Style

Ushio H, Ishibuchi S, Oshita K, Seki N, Kataoka H, Sugahara K, Adachi K, Chiba K. A New Phenylpyrazoleanilide, Y-320, Inhibits Interleukin 17 Production and Ameliorates Collagen-Induced Arthritis in Mice and Cynomolgus Monkeys. Pharmaceuticals. 2014; 7(1):1-17.

Chicago/Turabian Style

Ushio, Hiroyuki; Ishibuchi, Seigo; Oshita, Koichi; Seki, Noriyasu; Kataoka, Hirotoshi; Sugahara, Kunio; Adachi, Kunitomo; Chiba, Kenji. 2014. "A New Phenylpyrazoleanilide, Y-320, Inhibits Interleukin 17 Production and Ameliorates Collagen-Induced Arthritis in Mice and Cynomolgus Monkeys." Pharmaceuticals 7, no. 1: 1-17.



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