Basic medicinal chemistry in novel biologically active compounds based on behavioral regulation of protein

• Project/Area Number: 19790007
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Chemical pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: AOYAMA Hiroshi The University of Tokyo, 分子細胞生物学研究所, 助教 (40374699)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,060,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2007: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: 生理活性 / タンパク質 / 有機化学 / 光親和性標識 / 有機合成 / アミノ酸

Research Abstract

本研究ではタンパク質の行動制御という新しい医薬カテゴリーを提案し、その高次標的創薬手法を確立するために、細胞内のプロテアソーム分解、微小管重合阻害、血管新生阻害にターゲットを絞って研究を行った。その結果、3 つの標的全てにおいて小分子によるタンパク質の行動制御を達成でき、学術的にも興味深い知見を得ることができた。また、上記標的は全て抗がん剤開発への展開が可能であり、対象分野への応用研究が期待できる。

Research Products

• [Journal Article] Demonstration of Direct Binding of cIAP1 Degradation-promoting Bestatin Analogs to BIR3 Domain : Synthesis and Application of Fluorescent Bestatin Ester Analogs (2008)
  • Author(s): Shinichi Sato, Hiroshi Aoyama, Hiroyuki Miyachi, Mikihiko Naito, Yuichi Hashimoto
  • Journal Title: Bioorg. Med. Chem. Lett 18 Pages: 3354-3358
  • Peer Reviewed
• [Journal Article] Degradation-promoters of Cellular Inhibitor of Apoptosis Protein 1 Based on Bestatin and Actinonin (2008)
  • Author(s): Shinichi Sato, Masashi Tetsuhashi, Keiko Sekine, Hiroyuki Miyachi, Mikihiko Naito, Yuichi Hashimoto, Hiroshi Aoyama
  • Journal Title: Bioorg. Med. Chem 16 Pages: 4685-4698
  • Peer Reviewed
• [Journal Article] Fusarielin A as an Anti-angiogenic and Anti-proliferative Agent : Basic Biological Characterization (2008)
  • Author(s): Haruka Fujimoto, Hiroshi Aoyama, Tomomi Noguchi-Yachide, Yuichi Hashimoto, Hisayoshi Kobayashi
  • Journal Title: Chem. Pharm. Bull 56 Pages: 298-304
  • NAID: 110006622632
  • Peer Reviewed
• [Journal Article] Degradationpromoters of Cellular Inhibitor of Apoptosis Protein 1 Based on B estatin and Actinonin (2008)
  • Author(s): S. Sato, H. Aoyama et.al.
  • Journal Title: Bioorg. Med. Chem 16 Pages: 4685-4698
  • Peer Reviewed
• [Journal Article] Demonstration of direct binding of cIAP1 degradationpromoting bestatin analogs to BIR3 domain : synthesis and application of fluorescent bestatin ester analogs (2008)
  • Author(s): S. Sato, H. Aoyama et.al.
  • Journal Title: Bioorg. Med. Chem. Lett 18 Pages: 3354-3358
  • Peer Reviewed
• [Journal Article] Fusarielin A as an Anti-Angiogenic and Antiproliferative Agent: Its Basic Biological Characterization (2008)
  • Author(s): Haruka Fujimoto
  • Journal Title: Chem. Pharm. Bull. 56 Pages: 298-304
  • Peer Reviewed
• [Journal Article] Development of Tubulin-polymerization Inhibitors Based on the Thalidomide Skeleton (2007)
  • Author(s): Hiroshi Aoyama, Tomomi Noguchi, Takashi Misawa, Takanori Nakamura, Hiroyuki Miyachi, Yuichi Hashimoto, Hisayoshi Kobayashi
  • Journal Title: Chem. Pharm. Bull 55 Pages: 944-949
  • NAID: 110006278705
  • Peer Reviewed
• [Journal Article] Development of Tubulin-Polymerization Inhibitors Based on the Thalidomide Skeleton (2007)
  • Author(s): Hiroshi Aoyama
  • Journal Title: Chem. Phann. Bull. 55 Pages: 944-949
  • NAID: 110006278705
  • Peer Reviewed
• [Presentation] タンパク質寿命制御に立脚した新規アポトーシス誘導剤創製研究 (2008)
  • Author(s): 佐藤伸一、青山洋史、鉄橋正士、宮地弘幸、内藤幹彦、橋本祐一
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-27
• [Presentation] タンパク質寿命制御に立脚した新規アポトーシス誘導剤創製研究 (2008)
  • Author(s): 佐藤 伸一
  • Organizer: 日本薬学会 第128年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-27
• [Presentation] Fusarielin Aの生物活性とその分子基盤 (2008)
  • Author(s): 藤本悠、青山洋史、谷内出(野口)友美、橋本祐一、小林久芳
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-26
• [Presentation] Fusarielin Aの生物活性とその分子基盤 (2008)
  • Author(s): 藤本 悠
  • Organizer: 日本薬学会 第128年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-26
• [Presentation] cIAP1減少を介した新規アポトーシス誘導剤創製研究 (2007)
  • Author(s): 佐藤伸一、青山洋史、棚谷綾、内藤幹彦、宮地弘幸、橋本祐一
  • Organizer: 第26回メディシナルケミストリーシンポジウム
  • Place of Presentation: 相模原
  • Year and Date: 2007-11-28
• [Presentation] cIAP1減少を介した新規アポトーシス誘導剤の合成研究 (2007)
  • Author(s): 佐藤伸一、青山洋史、内藤幹彦、宮地弘幸、橋本祐一、棚谷綾
  • Organizer: 第33回反応と合成の進歩シンポジウム
  • Place of Presentation: 長崎
  • Year and Date: 2007-11-05
• [Presentation] Fusarielin Aの生物活性とその分子基盤 (2007)
  • Author(s): 藤本悠、青山洋史、谷内出(野口)友美、橋本祐一、小林久芳
  • Organizer: 第49回天然有機化合物討論会
  • Place of Presentation: 札幌
  • Year and Date: 2007-09-19
• [Patent(Industrial Property Rights)] 新規ヒドロキサム酸誘導体 (2007)
  • Inventor(s): 青山洋史他4名
  • Industrial Property Rights Holder: 東京大学
  • Industrial Property Number: 2007-266460
  • Filing Date: 2007-10-12
  • Overseas