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Development and Application of Cell Death Control Molecules

Planned Research

Project AreaHomeostatic Regulation by Various Types of Cell Death
Project/Area Number 26110004
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

SODEOKA Mikiko  国立研究開発法人理化学研究所, 開拓研究本部, 主任研究員 (60192142)

Co-Investigator(Kenkyū-buntansha) どど 孝介  国立研究開発法人理化学研究所, 開拓研究本部, 専任研究員 (20415243)
Project Period (FY) 2014-07-10 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥48,750,000 (Direct Cost: ¥37,500,000、Indirect Cost: ¥11,250,000)
Fiscal Year 2018: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2017: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2016: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2015: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2014: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Keywords細胞死 / ネクローシス / 構造活性相関 / 有機化学 / 酸化ストレス
Outline of Final Research Achievements

In general, cell death is classified into two major categories, apoptosis and necrosis, according to its morphological features. Apoptosis is associated with characteristic and regulated morphological changes, but necrosis results in cellular swelling and rupture of cell membrane, which could be induced by accidental physical injury. Therefore, only apoptosis was believed to be regulated, and necrosis had been considered as uncontrolled and accidental cell death. However, recent studies have revealed novel mechanisms for controlling necrosis.
We previously developed indolylmaleimide (IM) derivatives as novel inhibitors for oxidative-stress-induced necrosis. In this study, we have revealed unique cell death inhibition profile of IM derivatives and developed a water-soluble IM derivative IM-17, which showed cardioprotective effects in ischemia-reperfusion injury.

Academic Significance and Societal Importance of the Research Achievements

本研究は、古くは制御されない細胞死として研究対象とされて来なかったネクローシスに新たにスポットライトを当てた点、またその作用機序に独自に開発した阻害剤を用いてアプローチする点に学術的意義がある。さらに、虚血性心疾患を含む心疾患は、現在我が国のがんに続く第2位の死因となっており、IM化合物が虚血性心疾患に治療効果を示したことの社会的意義は高い。IM化合物はその治療薬リードとして期待されると共に、その作用機序解明により新たな治療法の開発にもつながる可能性が考えられる。

Report

(6 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (36 results)

All 2019 2018 2017 2016 2015 2014 Other

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 4 results) Presentation (27 results) (of which Int'l Joint Research: 10 results,  Invited: 22 results) Remarks (1 results)

  • [Journal Article] 虚血再灌流障害の細胞障害機序とその対策2018

    • Author(s)
      中尾周平, どど孝介, 袖岡幹子
    • Journal Title

      Coronary Intervention

      Volume: 14(6) Pages: 27-33

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Indolylmaleimide Derivative IM-17 Shows Cardioprotective Effects in Ischemia-Reperfusion Injury.2018

    • Author(s)
      Dodo K, Shimizu T, Sasamori J, Aihara K, Terayama N, Nakao S, Iuchi K, Takahashi M, Sodeoka M.
    • Journal Title

      ACS Med Chem Lett.

      Volume: 9 Issue: 3 Pages: 182-187

    • DOI

      10.1021/acsmedchemlett.7b00454

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hyperoxidation of ether-linked phospholipids accelerates neutrophil extracellular trap formation2017

    • Author(s)
      Yotsumoto Satoshi、Muroi Yuito、Chiba Tatsuya、Ohmura Rio、Yoneyama Maki、Magarisawa Megumi、Dodo Kosuke、Terayama Naoki、Sodeoka Mikiko、Aoyagi Ryohei、Arita Makoto、Arakawa Satoko、Shimizu Shigeomi、Tanaka Masato
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 16026-16026

    • DOI

      10.1038/s41598-017-15668-z

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structure–Activity Relationship Study of 3-Amino-2-indolyllactam Derivatives: Development of Inhibitors of Oxidative Stress-Induced Necrosis2016

    • Author(s)
      Kosuke Dodo, Kenji Hayamizu, Tadashi Shimizu, Mikko Sodeoka
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 64 Issue: 7 Pages: 886-898

    • DOI

      10.1248/cpb.c16-00259

    • NAID

      130005160020

    • ISSN
      0009-2363, 1347-5223
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Platinum-Catalyzed Friedel-Crafts-Type C–H Coupling–Allylic Amination Cascade to Synthesize 3,4-Fused Tricyclic Indoles2016

    • Author(s)
      Yuta Suzuki, Yuito Tanaka, Shun-ichi Nakano, Kousuke Dodo, Natsumi Yoda, Ken-ichi Shinohara, Kazuko Kita, Atushi Kaneda, Mikiko Sodeoka, Yasumasa Hamada, and Tetsuhiro Nemoto
    • Journal Title

      Chem. Eur. J.

      Volume: 22 Issue: 13 Pages: 4418-4421

    • DOI

      10.1002/chem.201600375

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Structure-activity relationship study of 3-amino-2-indolyllactam derivatives: Development of inhibitors of oxidative stress-induced necrosis2016

    • Author(s)
      Kosuke Dodo, Kenji Hayamizu, Tadashi Shimizu, Mikiko Sodeoka
    • Journal Title

      Chem. Pharm. Bull.

      Volume: 64

    • NAID

      130005160020

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 酸化ストレスによるネクローシス選択的阻害剤-細胞死研究への阻害剤の活用2016

    • Author(s)
      どど 孝介,袖岡 幹子
    • Journal Title

      実験医学増刊

      Volume: 34 Pages: 1055-1062

    • Related Report
      2015 Annual Research Report
  • [Journal Article] VDAC3 gating is activated by suppression of disulfide-bond formation between the N-terminal region and the bottom of the pore2015

    • Author(s)
      Masateru Okazaki, Katsue Kurabayashi, Miwako Asanuma, Yohei Saito, Kosuke Dodo, Mikiko Sodeoka
    • Journal Title

      Biochim. Biophys. Acta

      Volume: 1848 Issue: 12 Pages: 3188-3196

    • DOI

      10.1016/j.bbamem.2015.09.017

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] New Functional Group for Photoaffinity Labeling2019

    • Author(s)
      Mikiko Sodeoka
    • Organizer
      Asian Chemical Biology Initiative 2019 Yangon Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Alkyne-Tag Raman Imaging2019

    • Author(s)
      Mikiko Sodeoka
    • Organizer
      2019 Queenstown Molecular Biology Meetings in Shanghai
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development and Therapeutic Application of Indolylmaleimide Derivatives: Unique Inhibitors for Oxidative Stress-Induced Necrosis2018

    • Author(s)
      Kosuke Dodo and Mikiko Sodeoka
    • Organizer
      The 2nd International Conference on Food Nutrition & Safety and Medicinal Chemistry
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of CDC25A/B-selective Inhibitor RE442018

    • Author(s)
      Mikiko Sodeoka
    • Organizer
      Workshop on Frontiers in Phosphatase Research and Drug Discovery
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Alkyne-Tag Raman Imaging2018

    • Author(s)
      Mikiko Sodeoka
    • Organizer
      The 3rd A3 Roundtable Meeting on Chemical Probe Research Hub
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ケミカルプローブ:化学から生命科学へ2018

    • Author(s)
      袖岡幹子
    • Organizer
      第31回理化学研究所と産業界との交流会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 酸化ストレスにより誘導されるネクローシスの抑制剤開発と虚血性疾患への応用2018

    • Author(s)
      どど孝介
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Transition Metal Catalysis and Chemistry of Bioactive Molecules2017

    • Author(s)
      Mikiko Sodeoka
    • Organizer
      Arthur C. Cope Award Symposium at 254th ACS National Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] がん細胞選択的な細胞死誘導活性を有するγ-リノレン酸の機能性誘導体の創製2016

    • Author(s)
      福島 翔、平井 剛、佐藤綾人、田村結城、どど孝介、袖岡幹子
    • Organizer
      第6回CSJ化学フェスタ2016
    • Place of Presentation
      タワーホール船堀(東京・船堀)
    • Year and Date
      2016-11-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] 生命機能解明をめざしたプローブ分子の創製2016

    • Author(s)
      袖岡 幹子
    • Organizer
      第33回有機合成化学セミナー
    • Place of Presentation
      ヒルトンニセコビレッジ(北海道・ニセコ)
    • Year and Date
      2016-09-06
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 酸化ストレスにより誘導されるネクローシスへの化学的アプローチ2016

    • Author(s)
      袖岡 幹子
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(神奈川・横浜市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Turn-ON fluorescent affinity labeling using small bifunctional O-NBD unit2016

    • Author(s)
      Kosuke Dodo
    • Organizer
      2016 Queenstown Molecular Biology Meetings
    • Place of Presentation
      Shanghai (China)
    • Year and Date
      2016-03-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Chemical Approach to Oxidative Stress-induced Necrosis2016

    • Author(s)
      Mikiko Sodeoka
    • Organizer
      Asian Chemical Biology Initiative 2016 Jakarta Meeting
    • Place of Presentation
      Jakarta (Indonesia)
    • Year and Date
      2016-01-30
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 有機合成化学から生命科学へのアプローチ2016

    • Author(s)
      袖岡 幹子
    • Organizer
      第25回千葉大学大学院薬学研究院 薬友会生涯教育セミナー
    • Place of Presentation
      千葉大学(千葉・千葉市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 細胞死のメカニズム解明を目指したケミカルバイオロジー研究2016

    • Author(s)
      どど孝介
    • Organizer
      金沢大学若手講演会
    • Place of Presentation
      金沢大学(石川・金沢市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 非アルコール性脂肪性肝炎の病態形成における多様な細胞死の意義2015

    • Author(s)
      鶴崎 慎也、松田 道隆、どど 孝介、袖岡 幹子、宮島 篤、田中 稔
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会 合同大会
    • Place of Presentation
      神戸ポートアイランド(兵庫・神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 触媒的分子内フリーデル・クラフツ型アルキル化反応による新規3,4位縮環型三環性インドール骨格合成法の開発と生物活性評価2015

    • Author(s)
      鈴木 雄太,田中 唯人,仲野 駿一,どど 孝介,袖岡 幹子,濱田 康正,根本 哲宏
    • Organizer
      第34回メディシナルケミストリーシンポジウム
    • Place of Presentation
      幕張国際研修センター(千葉・千葉市)
    • Year and Date
      2015-11-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] スカンジウム触媒によるシクロブタン縮環ヘテロ環類の合成と抗腫瘍活性2015

    • Author(s)
      仲野 駿一、どど 孝介、袖岡 幹子、濱田 康正、根本 哲宏
    • Organizer
      第34回メディシナルケミストリーシンポジウム
    • Place of Presentation
      幕張国際研修センター(千葉・千葉市)
    • Year and Date
      2015-11-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] Chemical Approach to Oxidative Stress-Induced Necrotic Cell Death2015

    • Author(s)
      Mikiko Sodeoka
    • Organizer
      Japan-Australia Meeting on Cell Death
    • Place of Presentation
      Melbourne (Australia)
    • Year and Date
      2015-10-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 細胞死研究から新しいケミカルバイオロジー手法の開発へ2015

    • Author(s)
      袖岡 幹子
    • Organizer
      東京薬科大学セミナー
    • Place of Presentation
      東京薬科大学(東京・八王子市)
    • Year and Date
      2015-07-01
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] ネクローシス制御機構解明を目指したケミカルバイオロジー研究:蛍光turn-ON型アフィニティーラベル化法の開発2015

    • Author(s)
      どど 孝介
    • Organizer
      第15回日本蛋白質科学会年会
    • Place of Presentation
      あわぎんホール(徳島・徳島市)
    • Year and Date
      2015-06-24
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Development of Cell Death Control Molecules: Chemical Biology for Cell Death Research2015

    • Author(s)
      Kosuke Dodo
    • Organizer
      日本化学会第95春季年会アジア国際シンポジウム
    • Place of Presentation
      日本大学理工学部・船橋キャンパス(千葉・船橋市)
    • Year and Date
      2015-03-26
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 酸化ストレスにより誘導されるネクローシスの制御2015

    • Author(s)
      袖岡 幹子
    • Organizer
      第9回レドックス・ライフイノベーションシンポジウム
    • Place of Presentation
      理化学研究所横浜キャンパス(神奈川・鶴見)
    • Year and Date
      2015-03-12
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Development of BRET Measurement for VDAC in Living Cells to Evaluate the Oligomerization Status during Cell Death Induction2014

    • Author(s)
      Moon-Il Kang, Kosuke Dodo, Mikiko Sodeoka
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川・横浜市)
    • Year and Date
      2014-11-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] 細胞死制御化合物の開発2014

    • Author(s)
      袖岡 幹子
    • Organizer
      細胞死を起点とする生体制御ネットワークの解明 キックオフシンポジウム
    • Place of Presentation
      東京大学(東京・文京区)
    • Year and Date
      2014-11-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] ネクローシス制御分子の開発と作用機序2014

    • Author(s)
      袖岡 幹子
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都国際会館(京都・京都市)
    • Year and Date
      2014-10-15
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 酸化ストレス誘導性ネクローシスを制御する化合物の開発とその作用機序2014

    • Author(s)
      どど 孝介
    • Organizer
      第23回日本Cell Death学会学術集会
    • Place of Presentation
      東京医科歯科大学(東京・文京区)
    • Year and Date
      2014-07-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Remarks] 虚血性心疾患に保護効果を示す化合物を開発-新しい治療法の開発に期待-

    • URL

      http://www.riken.jp/pr/press/2018/20180221_1/

    • Related Report
      2017 Annual Research Report

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Published: 2014-11-20   Modified: 2020-03-30  

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