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Design and synthesis of active targeting boron carriers to tumor vascularization for boron neutron capture therapy

Research Project

Project/Area Number 19590102
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NAGASAWA Hideko  Gifu Pharmaceutical University, 薬学部, 教授 (90207994)

Co-Investigator(Kenkyū-buntansha) UEDA Satoshi  岐阜薬科大学, 薬学部, 助教 (50453056)
増永 慎一郎  京都大学, 原子炉実験所, 准教授 (80238914)
Co-Investigator(Renkei-kenkyūsha) MASUNAGA Shin-ichiro  京都大学, 原子炉実験所, 準教授 (80238914)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords医薬品分子設計 / 中性子捕捉療法 / ボロンキャリア / インテグリン受容体 / RGD / 中性子捕捉療法(BNCT) / 能動送達 / ボロンクラスタ / ホウ素中性子捕捉療法 / インテグリン / 新生血管
Research Abstract

硼素中性子捕捉療法(BNCT)の治療効果を向上させるために、固形がん微小環境における新生血管を標的とした腫瘍標的化ボロンキャリアの開発を行った。能動的標的指向化(active targeting)ユニットとして種々のがん細胞や新生血管に高発現しているavb3インテグリン受容体リガンドの環状RGDペプチドと種々のボロンクラスタのハイブリッド分子を設計・合成し、体内動態を解析した。その結果、臨床適用されているボロンクラスタであるBSHに比べて、腫瘍内濃度、腫瘍滞留時間及び血液・腫瘍内濃度比の改善が認められた。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (41 results)

All 2009 2008 2007

All Journal Article (17 results) (of which Peer Reviewed: 17 results) Presentation (19 results) Book (5 results)

  • [Journal Article] Significance of nitroimidazole compounds and hypoxia-induceble factor-1 for imaging tumor hypoxia2009

    • Author(s)
      Kizaka-Kondoh S., Nagasawa H.
    • Journal Title

      Cancer Science, 100 doi : 10.1111/j. 1349-7006. 2009. 01195. x

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Copper-catalyzed synthesis of benzoxazoles via a regioselective C-H functionalization/C-O bond formation under an air atmosphere2009

    • Author(s)
      Ueda S., Nagasawa H.
    • Journal Title

      J. Org. Chem 74

      Pages: 4272-4277

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] The novel hypoxic cellradiosensitizer, TX-1877 has antitumoractivity through suppression ofangiogenesis and inhibits liver metastasison xenograft model of pancreaticcancer2008

    • Author(s)
      Miyake K., Uto Y., Nagasawa H. Hori H. et.al.
    • Journal Title

      Cancer Letters 272

      Pages: 325-335

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and biological activity of 1-methyl-tryptophan-tirapazamine hybrids as hypoxia-targeting indoleamine 2, 3-dioxygenase inhibitors2008

    • Author(s)
      Nakashima H., Uto Y., Nakata E., Nagasawa H. Hori H. et.al.
    • Journal Title

      Bioorganic & Medicinal Chemistry 16

      Pages: 8661-8669

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] TX-2152 : a conformationally rigid and electron-rich diyne analogue of FTY720 with in vivo antiangiogenic activity2008

    • Author(s)
      Nakayama S., Uto Y., Nagasawa H. Hori H. et.al.
    • Journal Title

      Bioorganic & Medicinal Chemistry 16

      Pages: 7705-7714

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bretz W. ; Anti-inflammatory effects of a bioavailable compound, Artepillin C, in Brazilian propolis2008

    • Author(s)
      Paulino N., Abreu S.R., Uto Y., Nagasawa H. Hori H. et.al.
    • Journal Title

      European Journal of Pharmacology 587

      Pages: 296-301

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and biological activity of 1-methyl-tryptophan-tirapazamine hybrids as hypoxia-targeting indoleamine 2, 3-dioxygenase inhibitors.2008

    • Author(s)
      H. Nakashima
    • Journal Title

      Bioorganic & Medicinal Chemistry 16

      Pages: 8661-8669

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TX-2152 : a conformationally rigid and electron-rich diyne analogue of FTY720 with in vivo antiangiogenic activity.2008

    • Author(s)
      S. Nakayama
    • Journal Title

      Bioorganic & Medicinal Chemistry 16

      Pages: 7705-7714

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-inflammatory effects of a bioavailable compound, Artepillin C, in Brazilian propolis.2008

    • Author(s)
      Niraldo Paulino
    • Journal Title

      European Journal of Pharmacology 587

      Pages: 296-301

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The novel hypoxic cell radiosensitizer, TX-1877 has antitumor activity through suppression of angiogenesis and inhibits liver metastasis on xenograft model of pancreatic cancer2008

    • Author(s)
      K. Miyake
    • Journal Title

      Cancer Letters 272

      Pages: 325-335

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design, synthesis and radiosensitizing activities of sugar-hybrid hypoxic cell radiosensitizers2008

    • Author(s)
      Takashi Nakae
    • Journal Title

      Bioorganic & Medicinal Chemistry 16

      Pages: 675-682

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design of antiangiogenic hypoxic cell radiosensitizers:2-Nitroimidazoles containing a 2-aminomethylene-4-cyclopentene-1, 3-dione moiety2008

    • Author(s)
      Yoshihiro Uto
    • Journal Title

      Bioorganic & Medicinal Chemistry掲載確定 (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 解糖系代謝のエネルギー源となる単糖に対するがん細胞特異性:糖ハイブリッド低酸素細胞放射線増感剤/制癌剤の分子設計-Pharmacokinetic drug designのすすめ-2008

    • Author(s)
      宇都義浩
    • Journal Title

      放射線生物研究 43(1)

      Pages: 68-79

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dependency of the effect of a vascular disrupting agent on sensitivity to tirapazamine and gamma-ray irradiation upon the timing of its administration and tumor size, with reference to the effect on intratumor quiescent cells2007

    • Author(s)
      Masunaga S., Nagasawa H. Uto Y., Hori H., Ono K.
    • Journal Title

      J. Cancer Res. Clin. Oncol 133

      Pages: 47-55

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dependency of the effect of a vascular disrupting agent on sensitivity to tirapazamine and gamma-ray irradiation upon the timing of its administration and tumor size, with reference to the effect on intratumor quiescent cells2007

    • Author(s)
      Shin-Ichiro Masunaga
    • Journal Title

      J. Cancer Res. Clin. Oncol. 133

      Pages: 47-55

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The usefulness of mild temperature hyperthermia combined with continuous tirapazamine administration under reduced dose-rate irradiation with gamma-rays2007

    • Author(s)
      Shin-Ichiro Masunaga
    • Journal Title

      International Journal of Hyperthermia 23(1)

      Pages: 29-35

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of Molecular Chirality and Side Chain Bulkiness on Angiogenesis of Haloacetylcarbamoyl-2-nitroimidazole Compounds2007

    • Author(s)
      Ohkura Kazuto
    • Journal Title

      Anticancer Res. 27

      Pages: 3693-3700

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Development of new tumor targeting 10B-carrier : Boron cluster-cyclic RGD pentapeptide conjugates for boron neutron capture therapy2009

    • Author(s)
      Kimura S., Inaba Y., Kawamura Y., Masunaga S., Ueda S., Okuda K., Nagasawa H.
    • Organizer
      AACR 2009
    • Place of Presentation
      Colorado Denver
    • Related Report
      2008 Final Research Report
  • [Presentation] 低酸素イメージングを目指す近赤外蛍光バイオプローブの開発2009

    • Author(s)
      岡部泰之, 奥田健介, Bahaa YOUSSIF, 近藤科江, 上田聡, 永澤秀子
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都
    • Related Report
      2008 Final Research Report
  • [Presentation] 交差共役ケトン骨格を有する抗腫瘍性血管新生阻害剤の構造活性相関2009

    • Author(s)
      三原法秀, 林慧, 岡部泰之, 上田聡,奥田健介, 永澤秀子, 宇都義浩, 堀均
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都
    • Related Report
      2008 Final Research Report
  • [Presentation] チアゾリジンジオン骨格を有する新規選択的血管新生阻害剤GPU-4の開発2009

    • Author(s)
      林慧, 三原法秀, 岡部泰之, 上田聡, 奥田健介, 永澤秀子, 加来田博貴, 松永望, 原英彰
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都
    • Related Report
      2008 Final Research Report
  • [Presentation] 低酸素応答を標的としたブラジル産プロポリスの成分探索2009

    • Author(s)
      服部久範, 野田美奈絵, 上田聡, 奥田健介, 永澤秀子
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都
    • Related Report
      2008 Final Research Report
  • [Presentation] 低酸素領域を可視化する新規近赤外蛍光プローブの分子設計2009

    • Author(s)
      奥田健介, 岡部泰之, 上田聡, 永澤秀子, 近藤科江
    • Organizer
      第11回がん治療増感研究シンポジウム
    • Place of Presentation
      奈良
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] 低酸素イメージングを目指す近赤外蛍光バイオプローブの開発2009

    • Author(s)
      岡部 泰之
    • Organizer
      日本薬学会129年会
    • Place of Presentation
      京都
    • Related Report
      2008 Annual Research Report
  • [Presentation] 交差共役ケトン骨格を有する抗腫瘍性血管新生阻害剤の構造活性相関2009

    • Author(s)
      林 慧
    • Organizer
      日本薬学会129年会
    • Place of Presentation
      京都
    • Related Report
      2008 Annual Research Report
  • [Presentation] 低酸素応答を標的としたブラジル産プロポリスの成分探索2009

    • Author(s)
      服部 久範
    • Organizer
      日本薬学会129年会
    • Place of Presentation
      京都
    • Related Report
      2008 Annual Research Report
  • [Presentation] チアゾリジンジオン骨格を有する新規選択的血管新生阻害剤GPU-4の開発2009

    • Author(s)
      林 慧
    • Organizer
      日本薬学会129年会
    • Place of Presentation
      京都
    • Related Report
      2008 Annual Research Report
  • [Presentation] チアゾリジンジオン骨格を有する新規選択的血管新生阻害剤の開発2008

    • Author(s)
      永澤秀子, 林慧, 三原法秀, 岡部泰之,上田聡, 奥田健介, 加来田博貴, 松永望, 原英彰
    • Organizer
      第6回がんとハイポキシア研究会
    • Place of Presentation
      広島
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] Design, synthesis, and biological evaluation of cyclic imide derivatives as new potent angiogenesis inhibitors2008

    • Author(s)
      Nagasawa H., Hayashi K., Okabe Y., Suto T., Mihara N., Ueda S., Kakuta H.
    • Organizer
      AACR 2008
    • Place of Presentation
      San Diego
    • Related Report
      2008 Final Research Report
  • [Presentation] Design, synthesis, and biological evaluation of cyclic imide derivatives as new potent angiogenesis inhibitors2008

    • Author(s)
      林 慧
    • Organizer
      AACR 2008
    • Place of Presentation
      San Diego USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] 環状イミド構造を有する新規血管新生阻害剤の分子設計2008

    • Author(s)
      永澤 秀子
    • Organizer
      第14回国際癌治療増感研究会
    • Place of Presentation
      鈴鹿
    • Related Report
      2008 Annual Research Report
  • [Presentation] インテグリンを標的とする新規ボロンキャリアの分子設計2008

    • Author(s)
      木村 禎亮
    • Organizer
      第10回癌治療増感研究シンポジウム
    • Place of Presentation
      奈良市ならまちセンター
    • Related Report
      2007 Annual Research Report
  • [Presentation] 血管新生阻害及び転移抑制作用をめざすhypoxic cytotoxinの分子設計2008

    • Author(s)
      岩木 孝晴
    • Organizer
      日本薬学会 第128年会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] 環状イミド構造を有する新規血管新生阻害剤の分子設計2008

    • Author(s)
      林 慧
    • Organizer
      日本薬学会 第128年会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] 低酸素腫瘍を標的としたTirapazamineハイブリッド型新規IDO阻害剤の分子設計2008

    • Author(s)
      一久 和弘
    • Organizer
      日本薬学会 第128年会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] 硼素中性子捕捉療法を目指した新規含硼素化合物の設計と合成研究-薬物動態制御をめざした分子設計-2007

    • Author(s)
      木村 禎亮
    • Organizer
      第二回育薬研究センター教育フォーラム 第二回「育薬・創薬研究」セミナー
    • Place of Presentation
      グランヴェール岐山
    • Year and Date
      2007-12-22
    • Related Report
      2007 Annual Research Report
  • [Book] ハイポキシアを標的とした抗癌剤(実験医学)2009

    • Author(s)
      宇都義浩, 中田栄司, 永澤秀子, 堀均
    • Publisher
      羊土社
    • Related Report
      2008 Final Research Report
  • [Book] 実験医学2009

    • Author(s)
      宇都 義浩
    • Publisher
      羊土社
    • Related Report
      2008 Annual Research Report
  • [Book] 低酸素標的薬2007

    • Author(s)
      永澤秀子
    • Publisher
      実験医学、用度者
    • Related Report
      2008 Final Research Report
  • [Book] 実験医学2007

    • Author(s)
      永澤 秀子
    • Publisher
      羊土社
    • Related Report
      2007 Annual Research Report
  • [Book] 岐阜県病院薬剤師会雑誌2007

    • Author(s)
      永澤 秀子
    • Publisher
      岐阜県病院薬剤師会
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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