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Development of novel antitumor peptidomimetic drugs targeting Drs/SRPX tumor suppressor

Research Project

Project/Area Number 16K07169
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor therapeutics
Research InstitutionShiga University of Medical Science

Principal Investigator

Yukihiro Tambe  滋賀医科大学, 医学部, 助教 (50283560)

Research Collaborator INOUE Hirokazu  
KIM Chul-Jang  
TERADO Tokio  
NAKANO Hirofumi  
Project Period (FY) 2016-10-21 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords分子標的薬 / 抗腫瘍活性 / ペプチド模倣 / drs/SRPX / sushiモチーフ / 分子模倣 / 抗癌剤 / Drs癌抑制遺伝子 / Sushiモチーフ / 癌 / 生理活性 / 薬学 / 生体機能利用 / シグナル伝達
Outline of Final Research Achievements

Drs protein is the tumor suppressor gene product that is closely associated with the malignant transformation of human cancers. In this study, we examined the antitumor activity of MI compounds, which are the small molecular compounds that mimic the partial conformation of Drs. Screening with candidate compounds mimicking the Sushi domain of Drs led to the discovery of MI compounds suppressing human cancer cell lines such as pancreatic, colorectal, and bladder cancers at 10-40 micromolar. These compounds exerted antitumor effects through mechanisms such as apoptosis induction and invasion suppression. These results suggest that Drs may be a new molecular target for human cancer therapy.

Academic Significance and Societal Importance of the Research Achievements

近年、抗癌剤の進歩によって癌の治療成績は大幅に改善した。しかし再発や転移の問題、K-ras変異のある膵臓癌などの難治性癌、耐性獲得、抗癌剤の副作用など解決すべき課題は多く、従来とは異なる機構の抗癌剤開発の必要がある。本研究の成果はDrsが癌治療のための新しい分子標的になる可能性を示唆している。また、Sushiドメインを分子模倣することの有効性を見出したことから、他のSushiドメインを有するタンパク質(IL受容体やセレクチンなど)についても同様のアプローチが有効である可能性が示唆された。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (8 results)

All 2019 2018 2017 2016

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (4 results)

  • [Journal Article] Antitumor activity of potent pyruvate dehydrogenase kinase 4 inhibitors from plants in pancreatic cancer2019

    • Author(s)
      Tambe Y, Terado T, Kim CJ, Mukaisho K, Yoshida S, Sugihara H, Tanaka H, Chida J, Kido H, Yamaji K, Yamamoto T, Nakano G, Omura S, Inoue H
    • Journal Title

      Molecular Carcinogenesis

      Volume: 印刷中

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-oncogenic activities of cyclin D1b siRNA on human bladder cancer cells via induction of apoptosis and suppression of cancer cell stemness and invasiveness.2018

    • Author(s)
      Kim CJ, Terado T, Tambe Y, Mukaisho KI, Sugihara H, Kawauchi A, Inoue H.
    • Journal Title

      Int J Oncol.

      Volume: 52 Pages: 231-240

    • DOI

      10.3892/ijo.2017.4194

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Periostin suppresses in vitro invasiveness via PDK1/Akt/mTOR signaling pathway in a orthotopic model of bladder cancer.2017

    • Author(s)
      Kim, C. J., Tambe, Y., Mukaisho, K., Sugihara, H., Kageyama, S., Kawauchi, A., Inoue, H.
    • Journal Title

      Oncology Letters

      Volume: 13 Issue: 6 Pages: 4276-4284

    • DOI

      10.3892/ol.2017.6004

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Akt-dependent activation of Erk by cyclin D1b contributes to cell invasiveness and tumorigenicity.2016

    • Author(s)
      Kim CJ, Tambe Y, Mukaisho KI, Sugihara H, Kawauchi A, Inoue H.
    • Journal Title

      Oncology Letters

      Volume: 12 Issue: 6 Pages: 4850-4856

    • DOI

      10.3892/ol.2016.5286

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Anti-oncogenic activity of a novel PDK4 inhibitor in bladdercancer by suppressing the H-Ras and cancer stemness2018

    • Author(s)
      Chul Jang Kim, Tokio Terado, Yukihiro Tambe, Hirofumi Nakano, Akihiro Kawauchi, Hirokazu Inoue
    • Organizer
      第77回日本癌学会総会(大阪)
    • Related Report
      2018 Annual Research Report
  • [Presentation] Antitumor activity of a novel PDK4 inhibitor, cryptotanshinone,in pancreatic cancer by suppressing the KRAS expression2018

    • Author(s)
      Yukihiro Tambe, Tokio Terado, Chul Jang Kim, Hirofumi Nakano, Ken-ichi Mukaisho, Hiroyuki Sugihara, Hirokazu Inoue
    • Organizer
      第77回日本癌学会総会(大阪)
    • Related Report
      2018 Annual Research Report
  • [Presentation] Cyclin D1bトランスジェニックマウスにはSSA/P類似直腸腫瘍が発生する2017

    • Author(s)
      向所賢一、旦部幸博、金哲將、園田寛道、清水智治、谷眞至、杉原洋行、井上寛一
    • Organizer
      第86回大腸癌研究会
    • Place of Presentation
      盛岡市
    • Year and Date
      2017-01-20
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒト膵臓癌細胞株のin vivo造腫瘍能と癌幹細胞性に対するPDK4阻害剤の作用2017

    • Author(s)
      旦部幸博, 寺戸勅雄, 金哲將, 中野洋文, 向所賢一, 杉原洋行, 井上寛一
    • Organizer
      第76回日本癌学会学術総会(横浜)
    • Related Report
      2017 Research-status Report

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Published: 2016-10-24   Modified: 2020-03-30  

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