Target molecule analysis of the keloid therapeutic drug Tranilast and the development of a new molecule target keloid therapeutic drug

• Project/Area Number: 19592084
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Plastic surgery
• Research Institution: Tokyo Metropolitan Organization for Medical Research
• Principal Investigator: OGURA Kiyoshi Tokyo Metropolitan Organization for Medical Research, 東京都臨床医学総合研究所, 主任研究員 (70233492)
• Co-Investigator(Kenkyū-buntansha): KASAMA Takeshi 東京医科歯科大学, 機器分析センター, 准教授 (80124668)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 創傷治癒 / トラニラスト / ケロイド / 標的治療 / 薬学 / シグナル伝達

Research Abstract

ケロイドは、傷の部分が赤みを帯び、盛り上がり、痒み、痛みなどを伴う皮膚の病気で、傷を修復する線維芽細胞がコラーゲンを異常産生することに病因がある。ケロイド形成の主役を担うコラーゲンの異常産生にはTGF-βが関与する。Hgs蛋白はTGF-βシグナル伝達を促進する一方、Hgs蛋白のC領域はTGF-βシグナル伝達を阻害する。このC領域を構成するオリゴペプチドから新しいケロイド薬のリード化合物を検索し、ケロイド薬に求められる活性を有するオリゴペプチOP20-7を見いだした。

Research Products

• [Journal Article] Zebrafish and mouse alpha2, 3-sialyltransferases responsible for synthesizing GM4 ganglioside (2009)
  • Author(s): Chisada S., Yoshimura Y., Sakaguchi K., Uemura S., Go S., Ikeda K., Uchima H., Matsunaga N., Ogura K., Tai T., Okino N., Taguchi R., Inokuchi J., Ito M.
  • Journal Title: J Biol Chem. 284 Pages: 30534-30546
  • Peer Reviewed
• [Journal Article] Sulfatide is required efficient replication of Influenza A virus (2008)
  • Author(s): Takahashi T., Murakami K., Nagakura M., Kishita H., Watanabe S., Honke K., Ogura K., Tai T., Kawasaki K., Miyamoto D., Hidari KI., Guo CT., Suzuki Y., Suzuki T.
  • Journal Title: J Virol 82 Pages: 5940-5950
  • Peer Reviewed
• [Journal Article] SAR-oriented discovery of peroxisome proliferator-activated receptor pan agonist with a 4-adamantyl phenyl group as a hydrophobic tail (2008)
  • Author(s): Kasuga J., Yamasaki D., Ogura K., Shimizu M., Sato M., Makishima M., Doi T., Hashimoto Y., Miyachi H.
  • Journal Title: Bioorg. Med. Chem. Lett. 18 Pages: 1110-1115
  • Peer Reviewed
• [Journal Article] Sulfatide Is Required for Efficient Replication of Influenza A Virus (2008)
  • Author(s): Takahashi, T., Murakami, K., Nagakura, M., Kishita, H., Watanabe, S., Honke, K., Ogura, K., Tai, T., Kawasaki, K., Miyamoto, D., Hidari, K., I. P. J., Guo, C-T., Suzuki, Y., Suzuki T.
  • Journal Title: J. Virol. 82 Pages: 5940-5950
  • Peer Reviewed
• [Journal Article] Design, synthesis, and evaluation of isoindolinone-hydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors (2007)
  • Author(s): Lee S., Shinji C., Ogura K., Shimizu M., Maeda S., Sato M., Yoshida M., Hashimoto Y., Miyachi H.
  • Journal Title: Bioorg. Med. Chem. Lett. 17 Pages: 4895-4900
  • Peer Reviewed
• [Journal Article] Design, synthesis, and evaluation of isoindolinone-hydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors (2007)
  • Author(s): Lee, S., et al
  • Journal Title: Bioorg.Med.Chem.Lett. Volume: 17 Pages: 4895-4900
  • Peer Reviewed
• [Presentation] 精巣特異的に発現するPKCδ分子 (2008)
  • Author(s): 小倉潔, 新野由子, 塩田清二
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会 合同会議
  • Place of Presentation: 神戸
• [Presentation] 培養細胞系における管腔形成能評価のための画像解析の検討 (2008)
  • Author(s): 立野玲子, 小倉潔, 島村眞里子, 後藤敏行
  • Organizer: 日本バイオイメージング学会第17回学術集会
  • Place of Presentation: 千葉
• [Presentation] A novel PPAR alpha/beta/gamma-pan agonist inhibits cell growth in human pancreatic cancer cell lines (2008)
  • Author(s): Sato M., Yajima Y., Ogura K., Shimizu M., Nishitho Y., Miyachi H.
  • Organizer: The 67th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
• [Presentation] Analysis of antitumor activity of IL-2 (2008)
  • Author(s): Shimizu, M., Sato, M., Ogura, K., Nishito, Y., Takeda, Y., Mizuguchi, J., Yoshimoto, T.
  • Organizer: The 67th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
• [Presentation] Comprehensive gene expression analysis of melanoma B16 cells that Hgs expression level changed metastasis activity (2008)
  • Author(s): Ogura K., Kawashima I., Ishikawa Y., Sato M., Shimizu M., Takeda Y., Mizuguchi J., Yoshimoto T.
  • Organizer: The 67th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
• [Presentation] GEF-1/Hgs発現調節によりがん転移能の変化したマウスメラノーマB16細胞の網羅的遺伝子発現解析 (2008)
  • Author(s): 小倉潔, 川島育夫, 石川雄一郎, 島村眞理子, 佐藤眞友美, 清水元武
  • Organizer: 第17回日本がん転移学会学術集会
  • Place of Presentation: 鹿児島
• [Presentation] TIPP-703, a peroxisome proliferator-activated receptor pan agonist, induces a G1-phase arrest in human pancreatic carcinoma cell line (2008)
  • Author(s): Sato M., Yajima Y., Ogura K., Shimizu M., Miyachi H.
  • Organizer: The 33^<rd> FEBS Congress-11^<th> IUBMB Conference "Biochemistry of Xell Regulation"
  • Place of Presentation: Athens (Greece)
• [Presentation] Effects of Hgs on Metastasis ability of Mouse Melanoma B16 cells (2008)
  • Author(s): Ogura K., Kawashima I., Sato M., Shimizu M
  • Organizer: The 33^<rd> FEBS Congress-11^<th> IUBMB Conference "Biochemistry of Xell Regulation"
  • Place of Presentation: Athens (Greece)
• [Presentation] 新規PPARsリガンドによる膵がん細胞の細胞周期停止機構の名解明 (2008)
  • Author(s): 佐藤眞友美, 矢島由起子, 小倉潔, 西藤泰昌, 宮地弘幸
  • Organizer: 第81回日本内分泌学会学術総会
  • Place of Presentation: 青森
• [Presentation] Effects of Hgs on metastasis ability of mouse melanoma B16 cells (2008)
  • Author(s): Ogura. K., Kawashima, I., Sato, M., Shimizu, M.
  • Organizer: The 33rd FEBS Congress & 11th IUBMB Conference
  • Place of Presentation: Athens (Greece)
• [Presentation] TIPP-703, A peroxisome proliferator-activated receptor pan agonist, induces a g1-phase arrest in human pancreatic carcinoma cell lines (2008)
  • Author(s): Sato, M., Yajima Y., Ogura, K., Shimizu, M., Miyachi H.
  • Organizer: The 33rd FEBS Congress & 11th IUBMB Conference
  • Place of Presentation: Athens (Greece)
• [Presentation] マウスメラノーマB16細胞のがん転移能におけるHgs/GEF-1の影響 (2008)
  • Author(s): 小倉潔, 島村眞里子
  • Organizer: 第17回日本がん転移学会総会
  • Place of Presentation: 鹿児島
• [Presentation] Comprehensive gene expression analysis of melanoma B16 cells that Hgs expression level changed metastasis activity (2008)
  • Author(s): Ogura, K., Kawashima, I., Ishikawa, Y-I., Sato, M., Shimizu, M.
  • Organizer: The 67^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
• [Presentation] A novel PPAR alpha/beta/gamma-pan agonist inhibits cell growth in human pancreatic cancer cell lines (2008)
  • Author(s): Sato, M., Yajima Y., Ogura, K., Shimizu, M., Nishitho, Y., Miyachi H.
  • Organizer: The 67^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
• [Presentation] Hgs 高発現および抑制マウスメラノーマB16細胞の遺伝子発現プロファイリング (2007)
  • Author(s): 小倉潔, 佐藤眞友美, 清水本武
  • Organizer: 第30回日本分子生物学会年会・第80回生化学会大会合同大会
  • Place of Presentation: 横浜
• [Presentation] 画像解析による管腔形成能の評価 (2007)
  • Author(s): 立野玲子, 小倉潔, 島村眞里子, 後藤敏行
  • Organizer: 日本バイオイメージング学会第16回学術集会
  • Place of Presentation: 千葉
• [Presentation] Novel PPAR α, γ dual agonists induce a G1-phase arrest in pancreatic cancer cells (2007)
  • Author(s): Sato M., Ogura K., Shimizu M., Kunimasa K., Ohta T., Kaji K., Miyachi, H.
  • Organizer: The 66^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama
• [Presentation] Effects of RNA interference of GEF-1/Hgs on metastasis of mouse melanoma B16 cells (2007)
  • Author(s): Ogura K., Horiguchi S., Sato M., Shimizu M.
  • Organizer: The 66^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama
• [Presentation] Role of macrophages and neutrophils in antitumor activity of Fas ligand (CD95L)-expressing tumor (2007)
  • Author(s): Shimizu M, Sato M., Ogura K., Takeda Y., Mizuguchi J., Yoshimoto T.
  • Organizer: The 66^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama
• [Presentation] Molecular cloning and characterization of the novel 2, 3-sialyltransferase (GM4 synthase) from zebrafish. Insights into the glycosphingolipid receptor for fish vibriosis (2007)
  • Author(s): Chisada S., Yoshimura Y., Uchima H., Ogura K., Tai T., Okino N., Ito. M.
  • Organizer: 第27回日本糖質学会年会
  • Place of Presentation: 福岡
• [Presentation] マウスメラノーマB16細胞のがん転移能におけるHgs/GEF-1の影響 (2007)
  • Author(s): 小倉潔, 島村眞里子
  • Organizer: 第16回日本がん転移学会総会
  • Place of Presentation: 富山
• [Presentation] PPAR α γデュアルリガンドによる膵がん細胞の細胞周期調節作用 (2007)
  • Author(s): 佐藤眞友美, 小倉潔, 矢島由起子, 国政和宏, 太田敏郎, 宮地弘幸
  • Organizer: 第80回日本内分泌学術集会
  • Place of Presentation: 東京
• [Presentation] Novel PPAR α,γ dual agonists induce a G1-phase arrest in pancreatic cancer cells (2007)
  • Author(s): Sato, M., Ogura, K., Shimizu, M., Kunimasa, K., Ohta, T., Kaji, K., Miyachi., H.
  • Organizer: The 66^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama
• [Remarks]
  • URL: http://www.rinshoken.or.jp/
• [Remarks]
  • URL: http://www.rinshoken.or.jp/
• [Patent(Industrial Property Rights)] ガラクトシルセラミド発現因子-1を標的とする腫瘍増殖制御法 (2010)
  • Inventor(s): 財団法人東京都医学研究機構 小倉潔
  • Industrial Property Rights Holder: 財団法人東京都医学研究機構
  • Industrial Property Number: 2010-144763
  • Filing Date: 2010-06-25