Search for the inhibitors of the ubiquitin-activating enzyme (E1) as drug leads

• Project/Area Number: 26860067
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Natural medicines
• Research Institution: Kumamoto University
• Principal Investigator: Kawabata Tetsuro 熊本大学, 生命科学研究部, 助教 (70624873)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ユビキチン活性化酵素 (E1) / ユビキチン－プロテアソームシステム / 天然低分子化合物 / 抗がん剤 / ユビキチン-プロテアソームシステム / ユビキチン活性化酵素（Ｅ１） / ユビキチンープロテアソームシステム / 海洋無脊椎動物

Outline of Final Research Achievements

We have been searching for natural products, which inhibit the ubiquitin-proteasome system, as drug leads for treatment of cancer. In this project, we studied on the inhibitors of the ubiquitin-activating enzyme (E1). We prepared several derivatives of hyrtioreticulin A, which was isolated from the marine sponge as the E1 inhibitor by us, and examined the inhibitory activities of E1. Furthermore, we studied the biosynthetic pathway of the E1 inhibitor, himeic acid A, which was isolated from the fungus Aspergillus sp. isolated from the mussel by us.

Research Products

• [Int'l Joint Research] Sam Ratulangi University(Indonesia)
• [Int'l Joint Research] Naturalis Biodiversity Center(オランダ)
• [Journal Article] Niphateolide A: isolation from the marine sponge Niphates olemda and determination of its absolute configuration by an ECD analysis (2015)
  • Author(s): H. Kato, T. Nehira, K. Matsuo, T. Kawabata, Y. Kobashigawa, H. Morioka, F. Losung, R. E. P. Mangindaan, N. J. de Voogd, H. Yokosawa, S. Tsukamoto
  • Journal Title: Tetrahedron Volume: 71 Issue: 38 Pages: 6956-6960
  • DOI: 10.1016/j.tet.2015.07.009
  • NAID: 120006897988
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Acantholactam and pre-neo-kauluamine, manzamine-related alkaloids, from the Indonesian marine sponges, Acanthostrongylophora ingens. (2014)
  • Author(s): A. H. El-Desoky, H. Kato, K. Eguchi, T. Kawabata, Y. Fujiwara, F. Losung, R. E. P. Mangindaan, N. J. de Voogd, M. Takeya, H. Yokosawa, S. Tsukamoto
  • Journal Title: J. Nat. Prod. Volume: 77 Issue: 6 Pages: 1536-1540
  • DOI: 10.1021/np500290a
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Acanthomanzamines A-E with new manzamine frameworks from the marine sponge Acanthostrongylophora ingens. (2014)
  • Author(s): A. Furusato, H. Kato, T. Nehira, K. Eguchi, T. Kawabata, Y. Fujiwara, F. Losung, R. E. P. Mangindaan, N. J. de Voogd, M. Takeya, H. Yokosawa, S. Tsukamoto
  • Journal Title: Org. Lett. Volume: 16 Issue: 15 Pages: 3888-3891
  • DOI: 10.1021/ol5015569
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 1-Hydroxyethylhalenaquinone: a new proteasome inhibitor from the marine sponge Xestospongia sp. (2014)
  • Author(s): M. Yamakuma, H. Kato, K. Matsuo, A. H. El-Desoky, T. Kawabata, F. Losung, R. E. P. Mangindaan, N. J. de Voogd, H. Yokosawa, S. Tsukamoto
  • Journal Title: Heterocycles Volume: 89 Issue: 11 Pages: 2605-2610
  • DOI: 10.3987/com-14-13087
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Search for proteasome inhibitors from marine organisms (2015)
  • Author(s): Sachiko Tsukamoto, Ahmed H. El-Desoky, Akane Furusato, Michiko Yamakuma, Ai Noda, Eriko Sakai, Remy E. P. Mangindaan, Tetsuro Kawabata, Hikaru Kato
  • Organizer: ISPSA2015 TOKUSHIMA
  • Place of Presentation: 徳島（徳島文理大学）
  • Year and Date: 2015-08-30
  • Int'l Joint Research
• [Presentation] Xestospongia 属海綿から得られた新規プロテアソーム阻害物質 1-hydroxyethylhalenaquinone について (2014)
  • Author(s): 山隈理子、松尾佳苗、Ahmed H. Eldesoky、川畑哲郎、加藤光、塚本佐知子
  • Organizer: 第31回日本薬学会九州支部大会
  • Place of Presentation: 第一薬科大学（福岡）
  • Year and Date: 2014-12-06 – 2014-12-07
• [Presentation] 海綿 Petrosia corticata に含まれるメロテルペン strongylophorines の構造と活性 (2014)
  • Author(s): 野田愛、坂井恵理子、松尾佳苗、加藤光、川畑哲郎、塚本佐知子
  • Organizer: 第31回日本薬学会九州支部大会
  • Place of Presentation: 第一薬科大学（福岡）
  • Year and Date: 2014-12-06 – 2014-12-07
• [Presentation] 海綿 Acanthostrongylophora ingens から得られた新規 Manzamine 類縁体の構造と生物活性 (2014)
  • Author(s): 古里あかね、Ahmed Hamed El-Desoky、加藤光、江口啓介、藤原幸雄、川畑哲郎、竹屋元裕、塚本佐知子
  • Organizer: 第56回天然有機化合物討論会
  • Place of Presentation: 高知県立県民文化ホール（高知）
  • Year and Date: 2014-10-15 – 2014-10-17
• [Presentation] 海綿Petrosia corticata から得られた strongylophorines の生物活性 (2014)
  • Author(s): 野田愛、坂井恵理子、松尾佳苗、加藤光、川畑哲郎、塚本佐知子
  • Organizer: 日本生薬学会第61回年会
  • Place of Presentation: 福岡大学（福岡）
  • Year and Date: 2014-09-13 – 2014-09-14
• [Presentation] Xestospongia属海綿由来 halenaquinone 関連化合物によるプロテアソーム阻害活性について (2014)
  • Author(s): 山隈理子、松尾佳苗、Ahmed H. Eldesoky、川畑哲郎、加藤光、塚本佐知子
  • Organizer: 日本生薬学会第61回年会
  • Place of Presentation: 福岡大学（福岡）
  • Year and Date: 2014-09-13 – 2014-09-14
• [Remarks] 熊本大学大学院生命科学研究部天然薬物学分野ホームページ
  • URL: http://kumamoto-natmed.net/index.html
• [Remarks] 熊本大学大学院生命科学研究部天然薬物学分野
  • URL: http://kumamoto-natmed.net/