A New Phenylpyrazoleanilide, Y-320, Inhibits Interleukin 17 Production and Ameliorates Collagen-Induced Arthritis in Mice and Cynomolgus Monkeys
Abstract
:1. Introduction
2. Experimental Section
2.1. Chemistry
2.2. The General Procedure for the Synthesis of Y-320
2.3. Animals
2.4. IL-17 Production by CD4 T Cells Stimulated with IL-15
2.5. Generation of Th1 and Th17 Cells in Vitro
2.6. Phosphorylation of Janus Kinase (JAK) 1 and JAK3 by IL-15
2.7. CIA in DBA/1J Mice
2.8. CIA in Cynomolgus Monkeys
2.9. Real Time Polymerase Chain Reaction
2.10. Statistical Analysis
3. Results and Discussion
3.1. Y-320 Inhibits IL-17 Production by Murine and Human CD4 T Cells Stimulated with IL-15
3.2. Y-320 Ameliorates CIA in Mice with a Reduction of IL-17 mRNA in Arthritic Joints
3.3. Y-320 Shows Therapeutic Effects and a Synergistic Effect in Combination with Anti-TNF-α mAb on Chronic-Progressing CIA in Mice
3.4. Y-320 Shows Therapeutic Effects on CIA in Cynomolgus Monkeys
4. Conclusions
Acknowledgments
Conflicts of Interest
References
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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. https://doi.org/10.3390/ph7010001
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. https://doi.org/10.3390/ph7010001
Chicago/Turabian StyleUshio, Hiroyuki, Seigo Ishibuchi, Koichi Oshita, Noriyasu Seki, Hirotoshi Kataoka, Kunio Sugahara, Kunitomo Adachi, and Kenji Chiba. 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. https://doi.org/10.3390/ph7010001