Study of new IL-18 inhibitors and molecular targeting molecules for beta-trefoil cytokines

• Project/Area Number: 25461588
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Gifu University
• Principal Investigator: Kato Zenichiro 岐阜大学, 医学(系)研究科(研究院), 教授 (90303502)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: IL-18 / 立体構造 / 複合体 / 創薬

Outline of Final Research Achievements

The binding mode of IL-18 was determined at atomic resolution to investigate the complex structure of Il-18 ligand, Il-18 receptor alpha, and IL-18 receptor beta. The candidate drugs were obtained through the structural information. The candidates have different mode of inhibition from those we obtained before this study. The new molecular mechanism of the future drugs will open up a new avenue for drug development, especially for the beta-trefoil cytokines including IL-1,IL-18 and IL33.

Research Products

• [Journal Article] 患者によりそうサイエンス 先端科学と臨床現場をつなぐもの 構造医学からのアプローチ (2015)
  • Author(s): 加藤善一郎
  • Journal Title: 日本小児アレルギー学会誌 Volume: 29 Pages: 23-33
• [Journal Article] 蛋白質立体構造からみたIL-18のシグナル伝達メカニズムの解明 (2015)
  • Author(s): 木村 豪, 堤 尚孝, 有田 恭平, 有吉 眞理子, 山本 崇裕, 近藤 直実, 白川 昌宏, 杤尾 豪人, 加藤 善一郎
  • Journal Title: 呼吸 Volume: 34 Pages: 1056-1062
• [Journal Article] The structural basis for receptor recognition of human interleukin-18 (2014)
  • Author(s): Naotaka Tsutsumi, Takeshi Kimura, Kyohei Arita, Mariko Ariyoshi, Hidenori Ohnishi, Takahiro Yamamoto, Xiaobing Zuo, Katsumi Maenaka, Enoch Y. Park, Naomi Kondo, Masahiro Shirakawa, Hidehito Tochio and Zenichiro Kato
  • Journal Title: Nat. Commun. Volume: 5 5340 Issue: 1 Pages: 1-13
  • DOI: 10.1038/ncomms6340
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] For pediatric drug development; we can do 3D motion capture analysis (2015)
  • Author(s): Zenichiro Kato, Naoki Matsumaru.
  • Organizer: 3rd Gifu Inovation Lecture (International Symposium)
  • Place of Presentation: Gifu, Japan
  • Year and Date: 2015-10-08
  • Int'l Joint Research / Invited