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2012 Fiscal Year Final Research Report

SAR studies for epigenetic research based on natural product synthesis

Research Project

  • PDF
Project/Area Number 22590034
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical pharmacy
Research InstitutionUniversity of Shizuoka

Principal Investigator

HAMASHIMA Yoshitaka  静岡県立大学, 薬学部, 准教授 (40333900)

Project Period (FY) 2010 – 2012
Keywords天然物合成 / エピジェネティクス / ヒストンメチル化 / 構造活性相関 / Chaetocin / ジスルフィド結合
Research Abstract

The disorder of gene expression machinery is involved in various diseases including cancer. We have been focusing on controlling mechanism by selective methylation of histone protein that supports the structure of DNA as a novel target for drug discovery. In this study, we have developed an efficient method for the chemical synthesis of (+)-chaetocin, which is one of the promising inhibitors of histone methylation. This method allowed for the preparation of various analogs. Finally, we have succeeded in creating a novel and potent small molecule inhibitor of histone methyltransferase G9a, which is known to be responsible for cancerous diseases.

  • Research Products

    (15 results)

All 2013 2012 2011 2010 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (8 results) Remarks (1 results)

  • [Journal Article] Epidithiodiketopiperazine as a pharmacophore for protein lysine methyltransferase G9a inhibitors: Reducing cytotoxicity by structural simplification2013

    • Author(s)
      S. Fujishiro, K. Dodo, E. Iwasa, Y. Sohtome, Y. Hamashima, A. Ito, M. Yoshida, M. Sodeoka
    • Journal Title

      Bioorg. Med. Chem. Lett

      Volume: 23巻 Pages: 733-736

    • Peer Reviewed
  • [Journal Article] Synthesis and Biological Activities of Chaetocin and its Derivatives2012

    • Author(s)
      M. Sodeoka, K. Dodo, Y. Teng, K. Iuchi, Y. Hamashima, E. Iwasa, S. Fujishiro
    • Journal Title

      Pure Appl. Chem

      Volume: 84巻 Pages: 1369-1378

    • Peer Reviewed
  • [Journal Article] Epipolythiodiketopiperazine Alkaloids: Total Syntheses and Biological Activities2011

    • Author(s)
      E. Iwasa, Y. Hamashima, M. Sodeoka
    • Journal Title

      Israel J. Chem.

      Volume: 51巻 Pages: 420-433

    • Peer Reviewed
  • [Journal Article] Total syntheses of chaetocin and ent-chaetocin2011

    • Author(s)
      E. Iwasa, S. Fujishiro, Y. Hamashima, M. Sodeoka
    • Journal Title

      Tetrahedron

      Volume: 67巻 Pages: 6587-6599

    • Peer Reviewed
  • [Journal Article] Total Synthesis of (+)-Chaetocin and its Analogs: Their Histone Methyltransferase G9a Inhibitory Activity2010

    • Author(s)
      E. Iwasa, Y. Hamashima, S. Fujishiro, E. Higuchi, A. Ito, M. Yoshida, M. Sodeoka
    • Journal Title

      J. Am. Chem. Soc

      Volume: 132巻 Pages: 4078-4079

    • Peer Reviewed
  • [Journal Article] Unnatural enantiomer of chaetocin shows strong apoptosis-inducing activity through caspase-8/caspase-3 activation2010

    • Author(s)
      Y. Teng, K. Iuchi, E. Iwasa, S. Fujishiro, K. Dodo,Y. Hamashima, M. Sodeoka
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: 20巻 Pages: 5085-5088

    • Peer Reviewed
  • [Presentation] ヒストンメチル化酵素阻害剤Chaetocinの類縁体合成と構造活性相関研究2012

    • Author(s)
      藤城信哉, 岩佐江梨子, 滕玉鴎, 五月女宜裕, どど孝介, 濱島義隆, 樋口瑛介, 伊藤昭博, 吉田稔, 袖岡幹子
    • Organizer
      日本薬学会第132年会
    • Year and Date
      20120328-31
  • [Presentation] Synthesis of (+)-Chaetocin and Its Analogues: Investigation of Their Histone Methyltransferase Inhibitory Activity2011

    • Author(s)
      Y. Hamashima, E. Iwasa, S. Fujishiro, E. Higuchi, A. Ito, M. Yoshida, M. Sodeoka
    • Organizer
      AIMECS11
    • Place of Presentation
      東京
    • Year and Date
      2011-12-01
  • [Presentation] Total synthesis of (+)-Chaetocin and its analogs: Their structure-activity relationship studies for histone methyltransferaseG9a inhibitory activity2010

    • Author(s)
      E. Iwasa, Y. Hamashima, S. Fujishiro, E.Higuchi, A. Ito, M. Yoshida, M. Sodeoka
    • Organizer
      Pacifichem 2010
    • Place of Presentation
      Hawaii (USA)
    • Year and Date
      20101215-20
  • [Presentation] ヒストンメチル化酵素阻害剤 Chaetocin の構造活性相関研究2010

    • Author(s)
      藤城信哉, 岩佐江梨子, 濱島義隆, 樋口瑛介, 伊藤昭博, 吉田稔, 袖岡幹子
    • Organizer
      第29回メディシナルケミストリーシンポジウム
    • Place of Presentation
      京都
    • Year and Date
      20101117-19
  • [Presentation] Syntheses of (+)-chaetocin and its analogues and their histone methyltransferase inhibitory activity2010

    • Author(s)
      E. Iwasa, Y. Hamashima, S. Fujishiro, E. Higuchi, A. Ito, M. Yoshida, M. Sodeoka
    • Organizer
      RIKEN Symposium on 2010 RIKEN Chemical Biology International Symposium
    • Place of Presentation
      和光
    • Year and Date
      20101026-27
  • [Presentation] ヒストンメチル化阻害剤 (+)-Chaetocin および類縁体の合成と構造活性相関2010

    • Author(s)
      濱島義隆, 岩佐江梨子, 藤城信哉, 樋口瑛介, 伊藤昭博, 吉田稔, 袖岡幹子
    • Organizer
      第52回天然有機化合物討論会
    • Place of Presentation
      静岡
    • Year and Date
      20100929-10001
  • [Presentation] ヒストンメチル化阻害剤 (+)-Chaetocin および類縁体の合成と構造活性相関2010

    • Author(s)
      岩佐江梨子, 濱島義隆, 藤城信哉, 樋口瑛介, 伊藤昭博, 吉田稔, 袖岡幹子
    • Organizer
      日本ケミカルバイオロジー学会第五回年会
    • Place of Presentation
      東京
    • Year and Date
      20100518-19
  • [Presentation] ヒストンメチル化阻害剤 (+)-Chaetocin および類縁体の合成と構造活性相関2010

    • Author(s)
      濱島義隆, 岩佐江梨子, 藤城信哉, 樋口瑛介, 伊藤昭博, 吉田稔, 袖岡幹子
    • Organizer
      第9回新規素材探索研究会
    • Place of Presentation
      横浜
    • Year and Date
      2010-06-11
  • [Remarks]

    • URL

      http://www.riken.jp/r-world/research/lab/wako/organic/index.html

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Published: 2014-08-29  

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