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Development of zinc chelators to inhibit function of zinc protein participating in invasion and metastasis of cancer cell

Research Project

Project/Area Number 20590104
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Drug development chemistry
Research InstitutionKumamoto University

Principal Investigator

OKAMOTO Yoshinari  Kumamoto University, 大学院・生命科学研究部, 助教 (20194409)

Co-Investigator(Kenkyū-buntansha) OTSUKA Masami  熊本大学, 大学院・生命科学研究部, 教授 (40126008)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords癌 / 浸潤・転移 / 亜鉛キレーター / 亜鉛蛋白質
Research Abstract

Recently, it has been reported that transcription factor Snail, protease ADAM10 and ADAM17 are participating in invasion and metastasis of cancer cell. The present study aimed at development of specific inhibitors of these proteins. We are successful to synthesis a new pyridine/cysteamine based zinc chelator equipped with a marimastat side chain. This compound showed 80% inhibition against focus formation in 20 mM without any cell toxicity.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (36 results)

All 2011 2010 2009 2008

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (19 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Low direct cytotoxicity of loxoprofen on gastric mucosal cells2010

    • Author(s)
      Naoki Yamakawa, Shintaro Suemasu, Ayumi Kimoto, Yasuhiro Arai, Tomoaki Ishihara, Kazumi Yokomizo, Yoshinari Okamoto, Masami Otsuka
    • Journal Title

      Ken-ichiro Tanaka and Tohru Mizushima, Biol. Pharm. Bull. Vol.33

      Pages: 398-403

    • NAID

      130000248088

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Highly Sensitive Analysis of the Interaction between HIV-1 Gag and Phosphoinositide Derivatives Based on Surface Plasmon Resonance2010

    • Author(s)
      Kensaku Anraku, Ryota Fukuda, Nobutoki Takamune, Shogo Misumi, Yoshinari Okamoto, Masami Otsuka, Mikako Fujita
    • Journal Title

      Biochemistry Vol.49

      Pages: 5109-5116

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Properties and Synthesis of 2-{2-Fluoro (or Bromo)-4-[(2-oxocyclo pentyl)methyl]phenyl}propanoic acid : Nonsteroidal Antiinflmmatory Drugs withLow Membrane Permeabiliz- ing and Gastric Lesion-Producing Activities2010

    • Author(s)
      Naoki Yamakawa, Shintaro Suemasu, Masaaki Matoyama, Ayumi Kimoto, Miho Takeda, Ken-ichiro Tanaka, Tomoaki Ishihara, Takashi Katsu, Yoshinari Okamoto, Masami Otsuka, Tohru Mizushima
    • Journal Title

      J. Med. Chem. Vol.53

      Pages: 7879-7882

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of allergenicity of constituents of myoga using the murine local lymph node assay (LLNA)2010

    • Author(s)
      Qingjun Wei, Koichi Harada, Keiko Minamoto, Chang-Nian Wei, Yoshinari Okamoto, Masami Otsuka, Atsushi Ueda
    • Journal Title

      J. Immunopathology and pharmacology Vol.23

      Pages: 463-470

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Low direct cytotoxicity of loxoprofen on gastric mucosal cells2010

    • Author(s)
      N.Yamakawa
    • Journal Title

      Biol.Pharm.Bull.

      Volume: 33 Pages: 398-403

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Highly Sensitive Analysis of the Interaction between HIV-1 Gag and Phosphoinositide Derivatives Based on Surface Plasmon Resonance2010

    • Author(s)
      K.Anraku
    • Journal Title

      Biochemistry

      Volume: 49 Pages: 5109-5116

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Properties and Synthesis of 2-{2-Fluoro (or Bromo)-4-[(2-oxocyclopentyl)methyl]phenyl}propanoic acid : Nonsteroidal Antiinflmmatory Drugs with Low Membrane Permeabilizing and Gastric Lesion-Producing Activities2010

    • Author(s)
      N.Yamakawa
    • Journal Title

      J.Med.Chem.

      Volume: 53 Pages: 7879-7882

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Accerelated blood clearance phenomenon upon repeated injection of PEG-modified PLA-nanoparticles2009

    • Author(s)
      Tsutomu Ishihara, Miho Takeda, Haruka Sakamoto, Ayumi Kimoto, Chisa Kobayashi, Naoko Takasaki, Kanae Yuki, Ken-ichiro Tanaka, Mitsuko Takenaga, Rie Igarashi, Taishi Maeda, Naoki Yamakawa, Yoshinari Okamoto, Masami Otsuka, Tatsuhiro Ishida, Hiroshi Kiwada, Yutaka Mizushima, Tohru Mizushima
    • Journal Title

      Pharmaceut. Res. Vol.26

      Pages: 2270-2279

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of prostagrandin E1 phosphate derivatives and their encapsulation in biodegradable nanoparticle2009

    • Author(s)
      Miho Takeda, Taishi Maeda, Tsutomu Ishihara, Haruka Sakamoto, Kanae Yuki, Naoko Takasaki, Fumihiro Nishimura, Takeshi Yamashita, Ken-ichiro Tanaka, Mitsuko Takenaga, Rie Igarashi, Megumu Higaki, Naoki Yamakawa, Yoshinari Okamoto, Hisao Ogawa, Masami Otsuka, Yutaka Mizushima, Tohru Mizushima
    • Journal Title

      Pharmaceut. Res. Vol.26

      Pages: 1792-1800

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of prostagrandin E1 phosphate derivatives and their encapsulation in biodegradable nanoparticle2009

    • Author(s)
      M.Takeda
    • Journal Title

      Pharmaceut.Res. 26

      Pages: 1792-1800

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Accerelated blood clearance phenomenon upon repeated injection of PEG-modified PLA-nanoparticles2009

    • Author(s)
      T.Ishihara
    • Journal Title

      Pharmaceut.Res. 26

      Pages: 2270-2279

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design and synthesis of biotynylated inositol phosphate relevant to the biotin-avidin techniques2008

    • Author(s)
      Kensaku Anraku, Teruhiko Inoue, Kenji Sugimoto, Takashi Morii, Yasuo Mori, Yoshinari Okamoto, Masami Otsuka
    • Journal Title

      Org. Biomol. Chem. Vol.6

      Pages: 1822-1830

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of the indole core structures of conophylline2008

    • Author(s)
      Shin Ando, Yoshinari Okamoto, Kazuo Umezawa, Masami Otsuka
    • Journal Title

      J. Heterocycl. Chem. Vol.45

      Pages: 1803-1808

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Antiviral activities against herpes simplex virus type 1 by HPH derivatives and their structure-activity relationships2008

    • Author(s)
      Tetsuji Hosono, Kazumi Yokomizo, Akiyuki Hamasaki, Yoshinari Okamoto, Tadashi Okawara, Masami Otsuka, Ryozaburo Mukai, Keitaro Suzuki
    • Journal Title

      Bioorg. Med. Chem. Lett. Vol.18

      Pages: 371-374

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Design and synthesis of biotinylated inositol phosphate relevant to the biotin-avidin techniques2008

    • Author(s)
      K. Anraku
    • Journal Title

      Org. Biomol. Chem. 6

      Pages: 1822-1830

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of the indole core structures of conophylline2008

    • Author(s)
      S. Ando
    • Journal Title

      J. Heterocycl. Chem. 45

      Pages: 1803-1808

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 副作用を起こさない非ステロイド性抗炎症薬の創製2011

    • Author(s)
      山川直樹, 末益慎太郎, 勝孝, 岡本良成, 大塚雅巳, 水島徹
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      ツインメッセ静岡
    • Year and Date
      2011-03-31
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Systematic synthesis of all regioisomers of inositol phosphate2010

    • Author(s)
      Takashi Masuda, Kensaku Anraku, Kaori Sato, Yoshinari Okamoto, Masami Otsuka
    • Organizer
      Pacifichem2010
    • Place of Presentation
      Kamehameha Halls (Honolulu)U.S.A.
    • Year and Date
      2010-12-19
    • Related Report
      2010 Final Research Report
  • [Presentation] Systematic synthesis of all regioisomaers of inositol phosphate2010

    • Author(s)
      舛田岳史
    • Organizer
      Pacifichem 2010
    • Place of Presentation
      Kamehameha Halls(Honolulu, Hawaii USA)
    • Year and Date
      2010-12-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] 新規DNA切断分子の合成研究2010

    • Author(s)
      坂本慎弥, 松本正裕, 岡本良成, 大塚雅巳
    • Organizer
      第27回日本薬学会九州支部大会
    • Place of Presentation
      長崎大学
    • Year and Date
      2010-12-12
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] イノシトールリン酸類における全位置異性体の系統的合成法の開拓2010

    • Author(s)
      舛田岳史, 安楽健作, 佐藤かおり, 岡本良成, 大塚雅巳
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      桃太郎アリーナ(岡山)
    • Year and Date
      2010-03-29
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] 脳虚血後の脳保護に関与するPI3K-Akt経路を標的としたミオイノシトール誘導体の合成2010

    • Author(s)
      工藤康太, 安楽健作, 岡本良成, 藤田美歌子, 河野隆幸, 森岡基浩, 倉津純一, 大塚雅巳
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      桃太郎アリーナ(岡山)
    • Year and Date
      2010-03-29
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] ADAMファミリーメタロプロテアーゼ選択的阻害剤の合成研究2009

    • Author(s)
      大場誉徳, 井上奈月, 穴井美里, 岡本良成, 佐谷秀行, 大塚雅巳
    • Organizer
      第26回日本薬学会九州支部大会
    • Place of Presentation
      九州大学
    • Year and Date
      2009-12-13
    • Related Report
      2010 Final Research Report
  • [Presentation] ADAMファミリーメタロプロテアーゼ選択的阻害剤の合成研究2009

    • Author(s)
      大場誉徳
    • Organizer
      第26回日本薬学会九州支部大会
    • Place of Presentation
      九州大学(福岡)
    • Year and Date
      2009-12-13
    • Related Report
      2009 Annual Research Report
  • [Presentation] RANKを三量体化させる人工低分子化合物の開発とそれによるシグナル伝達制御システム構築の試み2009

    • Author(s)
      廣田真由子, 入江佳奈子, 小田一貴, 岡本良成, 合田仁, 井上純一郎, 藤田美歌子, 大塚雅巳
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-12-11
    • Related Report
      2010 Final Research Report
  • [Presentation] ADAMファミリーメタロプロテアーゼ特異的阻害剤の合成研究2009

    • Author(s)
      大場誉徳, 井上奈月, 穴井美里, 岡本良成, 佐谷秀行, 大塚雅巳
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都国際会館
    • Year and Date
      2009-03-28
    • Related Report
      2010 Final Research Report
  • [Presentation] ADAMファミリーメタロプロテアーゼ特異的阻害債の合成研究2009

    • Author(s)
      大場 誉徳
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都国際会館
    • Year and Date
      2009-03-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] イノシトールリン酸類における全位置異性体の系統的合成法の開拓2009

    • Author(s)
      舛田岳史, 安楽健作, 佐藤かおり, 岡本良成, 大塚雅巳
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都国際会館
    • Year and Date
      2009-03-26
    • Related Report
      2010 Final Research Report
  • [Presentation] HIV-1 Vif阻害剤を指向した亜鉛キレーターの合成と活性評価2009

    • Author(s)
      江島智彦, 岡本良成, 大塚雅巳, 藤田美歌子
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都国際会館
    • Year and Date
      2009-03-26
    • Related Report
      2010 Final Research Report
  • [Presentation] イノシトールリン酸類における全位置異性体の系統的合成法の開拓2009

    • Author(s)
      舛田 岳史
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都国際会館(京都)
    • Year and Date
      2009-03-26
    • Related Report
      2008 Annual Research Report
  • [Presentation] HIV-1 Vif阻害剤を指向した亜鉛キレーターの合成と活性評価2009

    • Author(s)
      江島 智彦
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都国際会館(京都)
    • Year and Date
      2009-03-26
    • Related Report
      2008 Annual Research Report
  • [Presentation] DHMEQ類似体の合成研究2008

    • Author(s)
      野田陽平, 岡本良成, 梅澤一夫, 大塚雅巳
    • Organizer
      第25回日本薬学会九州支部大会
    • Place of Presentation
      九州保健福祉大学(宮崎)
    • Year and Date
      2008-12-07
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] ADAMファミリーメタロプロテアーゼ特異的阻害剤の合成研究2008

    • Author(s)
      大場誉徳, 井上奈月, 穴井美里, 岡本良成, 大塚雅巳
    • Organizer
      第25回有機合成化学セミナー
    • Place of Presentation
      阿蘇プラザホテル(熊本)
    • Year and Date
      2008-09-08
    • Related Report
      2010 Final Research Report
  • [Presentation] ADAMファミリーメタロプロテアーゼ特異的阻害債の合成研究2008

    • Author(s)
      大場 誉徳
    • Organizer
      第25回有機合成化学セミナー
    • Place of Presentation
      阿蘇プラザホテル(熊本)
    • Year and Date
      2008-09-08
    • Related Report
      2008 Annual Research Report
  • [Presentation] がんに関わる生体反応を標的としたDNA切断分子の合成研究2008

    • Author(s)
      岡本良成, 松本正裕, 藤田美歌子, 大塚雅巳
    • Organizer
      第12回がん分子標的治療研究会総会
    • Place of Presentation
      学術総合センター(東京)
    • Year and Date
      2008-06-26
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Patent(Industrial Property Rights)] ロキソプロフェン誘導体及びそれを含有する医薬2009

    • Inventor(s)
      水島徹,大塚雅巳,岡本良成,山川直樹
    • Industrial Property Rights Holder
      国立大学法人熊本大学,株式会社LTTバイオファーマ
    • Industrial Property Number
      2009-043801
    • Filing Date
      2009-02-26
    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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