New Treatment Strategies for Inflammatory Bowel Disease using a novel NF-κB inhibitior (DHMEQ)

• Project/Area Number: 22591474
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Hokkaido University
• Principal Investigator: SUZUKI Tomomi 北海道大学, 大学院・医学研究科, 特任准教授 (70374238)
• Co-Investigator(Kenkyū-buntansha): YAMASHITA Kenichiro 北海道大学, 大学院・医学研究科, 特任准教授 (00399940)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 炎症性腸疾患 / 腸管免疫 / NF-κB / DTCM-G / マクロファージ / GSK-3β / AKT / NFκB

Research Abstract

A novel NF-κB inhibitor, DHMEQ, strongly ameliorated development of two types of experimental colitis in mice (DSS colitis and TNBS colitis) and DHMEQ appears as a promising candidate for treatment of inflammatory bowel disease. On the otherhand, we explored the development of another stronger NF-κB inhibitor and got3-[(dodecylthiocarbonyl)-methyl]-glutarimide (DTCM-G). We also demonstrated DTCM-G notably attenuated two types of experimental murine models of IBD. We investigated the underlying mechanism in the anti-inflammatory effect of DTCM-G by using RAW264.7 cellsand demonstrated that the inhibition of AKT and GSK-3β activations were related with theanti-inflammatory effect of DTCM-G.

Research Products

• [Journal Article] A novel NF-kB inhibitor, dehydroxymethylepoxyquinomicin, ameliorates inflammatory colonic injury in mice (2012)
  • Author(s): Funakoshi T, Yamashita K, Ichikawa N, Fukai M, Suzuki T, Goto R, Oura T, Kobayashi N, Katsurada T, Ichihara S, Ozaki M, Umezawa K, Todo S
  • Journal Title: Journal of Crohn's and Colitis Volume: 6 Pages: 215-225
  • Peer Reviewed
• [Journal Article] A novel NF-kB inhibitor, dehydroxymethylepoxyquinomicin,ameliorates inflammatory colonic injury in mice (2012)
  • Author(s): Funakoshi T, et al.
  • Journal Title: Journal of Crohn's and Colitis Volume: 6 Issue: 2 Pages: 215-225
  • DOI: 10.1016/j.crohns.2011.08.011
  • Peer Reviewed
• [Presentation] A Novel Anti-Inflammatory Agent, 3-[(dodecylthiocarbonyl)-methyl]-glutar imide, Ameliorates Murine Models of Inflammatory Bowel Disease (2011)
  • Author(s): Ichikawa N, Yamashita K, Funakoshi T, Shibasaki S, Ichihara S, Kobayashi N, Koshizuka Y, Zaitsu M, Fukai M, Suzuki T, Ozaki M, Umezawa K, Todo S
  • Organizer: Digestive Disease Week
  • Place of Presentation: McCormick Place, Chicago, US
• [Presentation] A Novel Anti-Inflammatory Agent,3-[(dodecylthiocarbonyl)-methyl]-glutar imide, Ameliorates Murine Models of Inflammatory Bowel Disease (2010)
  • Author(s): Ichikawa N, Yamashita K, Funakoshi T, Ichihara S, Kobayashi N, Koshizuka Y, Zaitsu M, Ogura M, Yoshida T, Tsunetoshi Y, Fukai M, Suzuki T, Ozaki M, Umezawa K, Todo S
  • Organizer: The 25th ISUCRS Biennial Congress
  • Place of Presentation: Palazzo della Cultura e dei Congressi, Bologna, Italy
• [Presentation] A Novel Anti-Inflammatory Agent, DTCM-Glutarimide (2010)
  • Author(s): Ichikawa N, Yamashita K, Funakoshi T, Shibasaki S, Ichihara S, Fukai M, Suzuki T, Ozaki M, Umezawa K, Todo S
  • Organizer: AttenuatesExperimental Colitis in Mice Digestive Disease Week
  • Place of Presentation: Morial Convention Center, New Orleans, US
• [Presentation] A novel NF-□B i nhi bit or , DHMEQ, ameliorates inflammatory colonic injuries in mice. (2010)
  • Author(s): Funakoshi T, Yamashita K, Ichikawa N,Kobayashi N, Fukai M, Suzuki T, Goto R, Oura T, Katsurada T, Ozaki M, Umezawa K, Todo S.
  • Organizer: Digestive Disease Week 2010
  • Place of Presentation: Morial ConventionCenter, New Orleans, US
• [Presentation] 炎症性腸疾患モデルに対するDTCM-glutarimideの効果に関する検討 (2010)
  • Author(s): 市川伸樹、山下健一郎、船越徹、柴崎晋、深井原、尾崎倫孝、梅澤一夫、藤堂省
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋、名古屋国際会議場
• [Presentation] 新規NF-κB阻害剤DHMEQの大腸炎モデルにおける炎症抑制作用 (2010)
  • Author(s): 舩越徹、市川伸樹、山下健一郎、深井原、鈴木友己、桂田武彦、後藤了一、大浦哲、小林希、尾崎倫孝、梅澤一夫、藤堂省
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋,名古屋国際会議場
• [Presentation] The therapeutic effect of a novelNF-□B inhibitor, DHMEQ, on experimentalcolitis in mice. (2010)
  • Author(s): Funakoshi T, Yamashita K, Ichikawa N, Kobayashi N, Fukai M, Suzuki T, Goto R, Oura T, Katsurada T, Ozaki M, Umezawa K, Todo S.
  • Organizer: The 24th ISUCRS Biennial Congress
  • Place of Presentation: COEX, Seoul, Korea
• [Presentation] 新規NF-κB阻害剤DHMEQのDSS誘発大腸炎抑制効果 (2009)
  • Author(s): 舩越徹、山下健一郎、深井原、鈴木友巳、木本好美、長山紘明、後藤了一、大浦哲、梅澤一夫、尾崎倫孝、藤堂省
  • Organizer: 第109回日本外科学会定期学術集会
  • Place of Presentation: 福岡、福岡国際会議場
  • Year and Date: 2009-04-24
• [Presentation] 炎症性腸疾患モデルにおける新規化合物DTCM-Gの腸炎抑制効果に関する検討
  • Author(s): 市川伸樹、山下健一郎、舩越徹、吉田雅、小林希、腰塚靖之、財津雅昭、柴崎晋、常俊雄介、小倉正臣、深井原、市原真、尾崎倫孝、梅澤一夫、藤堂省
  • Organizer: 第111回日本外科学会定期学術集会