Development of novel antitumor peptidomimetic drugs targeting Drs/SRPX tumor suppressor
| Project/Area Number |
16K07169
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor therapeutics
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
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| Research Collaborator |
INOUE Hirokazu
KIM Chul-Jang
TERADO Tokio
NAKANO Hirofumi
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| Project Period (FY) |
2016-10-21 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(8 results)
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[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
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Journal Title
Molecular Carcinogenesis
Volume: 印刷中
Related Report
Peer Reviewed
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[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.
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Journal Title
Oncology Letters
Volume: 13
Issue: 6
Pages: 4276-4284
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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