Development of novel antitumor drugs targeting activated Ras by protein knockdown

• Project/Area Number: 23890251
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Drug development chemistry
• Research Institution: National Institute of Health Sciences
• Principal Investigator: HATTORI Takayuki 国立医薬品食品衛生研究所, 機能生化学部, 主任研究官 (50377751)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: Ras / 癌 / 分子標的治療 / タンパク質分解

Research Abstract

In this study, we are developing the SNIPERs that specifically target activated mutant Ras proteins. We demonstrated that proliferation of tumor cells harboring activated mutant Ras was inhibited by ablation of mutant Ras. Furthermore, we identified some Ras-binding compounds as a ligand of SNIPER. We are now synthesizing bestatin-Ras-binding compounds hybrid (SNIPER).

Research Products

• [Presentation] 細胞膜透過性蛍光 NTA の設計・合 成 (2013)
  • Author(s): 加藤 雅士,正田 卓司,出水 庸介,井 上 英史,服部 隆行,内藤 幹彦,栗原 正 明
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜市
• [Presentation] 細胞分化に伴うRBタンパク質のセリン612の特異異的リン酸化. (2013)
  • Author(s): 服部 隆行,内田 千晴,高橋 宏隆,山 本 直樹,内藤 幹彦,田矢 洋一
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜市
• [Presentation] Distinct phosphorylation of the retinoblastoma protein at serine 612 in differentiated cells (2013)
  • Author(s): Takayuki Hattori, Chiharu Uchida, Hirotaka Takahashi, Naoki Yamamoto, Mikihiko Naito, Yoichi Taya.
  • Organizer: Ninth AACR/JCA Joint Conference
  • Place of Presentation: Hawaii, U S A
• [Presentation] Development of SNIPER(ER) that induces estrogen receptor degradation followed by rapidcell death in breast cancer cells (2013)
  • Author(s): Keiichiro Okuhira, Yosuke Demizu, Nobumichi Ohoka, Norihito Shibata, Takayuki Hattori, Tomoko Nishimaki-Mogami, Masaaki Kurihara, Haruhiro Okuda, Mikihiko Naito.
  • Organizer: Ninth AACR/JCA Joint Conference
  • Place of Presentation: Hawaii, U S A
• [Presentation] 細胞膜透過性蛍光NTAの創製 (2012)
  • Author(s): 正田 卓司,加藤 雅士,井上 英史,服 部 隆行,内藤 幹彦,栗原 正明.
  • Organizer: 第56回日本薬学会関東支部大会
  • Place of Presentation: 東京都
• [Presentation] 分化細胞におけるRB タンパク質のserine612 の部位特異的リン酸化 (2012)
  • Author(s): 服部隆行,田矢洋一
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌市
• [Presentation] プロテインノックダウン法によるエストロゲンレセプターの分解 (2012)
  • Author(s): 奥平 桂一郎,出水 庸介,大岡 伸通, 柴田 識人,服部 隆行,最上(西巻) 知 子,栗原 正明,奥田 晴宏,内藤 幹彦
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌市
• [Presentation] シガトキシンBサブユニットによる細胞死誘導機構 (2012)
  • Author(s): 服部 隆行,大岡 伸通,高橋 美帆,西 川 喜代孝,内藤 幹彦
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌市
• [Presentation] Development of Hybrid Small Molecules That Induce IAP-Mediated Ubiquitylation and Proteasomal Degradation of Target Proteins in a Specific Manner (2012)
  • Author(s): Mikihiko Naito, Keiichiro Okuhira, Yosuke Demizu, Yukihiro Itoh, Minoru Ishikawa, Nobumichi Ohoka, Norihito Shibata, Takayuki Hattori, Tomoko Nishimaki-Mogami, Masaaki Kurihara, and Yuichi Hashimoto
  • Organizer: Genetics and Chemistry Sharing a Language of Discovery
  • Place of Presentation: Boston, USA
• [Presentation] Degradation of Estrogen Receptor Induced by a Small Hybrid Molecule SNIPER (ER) (2012)
  • Author(s): Keiichiro Okuhira, Yosuke Demizu, Nobumichi Ohoka, Norihito Shibata, Takayuki Hattori, Tomoko-Nishimaki Mogami, Masaaki Kurihara, Haruhiro Okuda, and Mikihiko Naito
  • Organizer: The 16th Japanese Foundation for Cancer Research-International Symposium on Cancer Chemotherapy
  • Place of Presentation: Tokyo
• [Presentation] プロテインノックダウン法によるエストロゲン受容体の分解 (2011)
  • Author(s): 奥平 桂一郎,出水 庸介,大岡 伸通, 柴田 織人,服部 隆行,最上(西巻)知子,栗原 正明,奥田 晴宏,内藤 幹彦
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋市
• [Remarks]
  • URL: http://www.nihs.go.jp/dfbg/frame.html