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Identification of novel compounds from original chemical libraries affecting autoimmune diseases.

Research Project

Project/Area Number 18K06895
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48030:Pharmacology-related
Research InstitutionNagasaki University

Principal Investigator

Yonezawa Tomo  長崎大学, 医歯薬学総合研究科(薬学系), 准教授 (60515964)

Co-Investigator(Kenkyū-buntansha) 倉田 里穂  大阪薬科大学, 薬学部, 助教 (70711729)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords自己免疫疾患 / NFkB / IRF / SEAP / HTS / IL-18 / IRF転写活性 / NFkB転写活性 / 独自ライブラリー / ハイスループットスクリーニング / IL-18シグナル / 新規リポーター細胞 / I型インターフェロン応答 / 化合物ライブラリー / 多発性硬化症
Outline of Final Research Achievements

We recently have established the cells stably expressing IRF- or NFkB-driven human secreted embryonic alkaline phosphatase (SEAP) by episomal vector, which can maintain constructs synchronized to host cell replication. We also introduced an another construct stably expressing two IL-18 receptor sub units and then, can monitor IL-18 specifically activated NFkB. Then, we demonstrated high-throughput screening by the novel reporter cells from natural extracts, which are derived from Chinese herb medicine plants, fungi or marine bacteria, or synthetic compounds, which are gifted from Japanese organic synthetic chemists. Finally, we identified several extracts and compounds affecting IRF- or NFkB-activation.

Academic Significance and Societal Importance of the Research Achievements

培養細胞へエピソーマル型ベクターを用いて、恒常的に、NFkBまたはIRF制御下でSEAPを発現および分泌するリポーターを導入し、新規リポーター細胞を樹立し、ドラッグスクリーニングが可能な高感度および確度を持つ測定系を実現した。さらに、樹立したNFkB-SEAPリポーター細胞へ、IL-18受容体遺伝子を同様に導入し、IL-18特異的なNFkBを検出できるリポーター細胞およびアッセイ系も樹立した。最終的に、樹立したリポーター細胞を用いたドラッグスクリーニングにより、独自ライブラリーから薬効を保持する抽出物および化合物を同定した。抗がん剤および自己免疫疾患の治療薬創出に繋がる有意義な結果である。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (18 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (3 results) Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (6 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Book (5 results)

  • [Int'l Joint Research] Wuhan University of Technology(中国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Wuhan University of Technology(中国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Wuhan University of Technology(中国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Establishment of Novel Protein Interaction Assays between Sin3 and REST Using Surface Plasmon Resonance and Time-Resolved Fluorescence Energy Transfer2021

    • Author(s)
      Harada, M., Nagai, J., Kurata, R., Cui, X., Isagawa, T., Semba, H., ... & Yonezawa, T.
    • Journal Title

      International journal of molecular sciences

      Volume: 22(5) Issue: 5 Pages: 2323-2323

    • DOI

      10.3390/ijms22052323

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel Reporter System Monitoring IL-18 Specific Signaling Can Be Applied to High-Throughput Screening2020

    • Author(s)
      Kurata R, Shimizu K, Cui X, Harada M, Isagawa T, Semba H, Ishihara J, Yamada K, Nagai J, Yoshida Y, Takeda N, Maemura K, Yonezawa T.
    • Journal Title

      Marine Drugs

      Volume: 18 Issue: 1 Pages: 60-60

    • DOI

      10.3390/md18010060

    • NAID

      120006988310

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Establishment of Novel High-Standard Chemiluminescent Assay for NTPase in Two Protozoans and Its High-Throughput Screening2020

    • Author(s)
      Masamitsu Harada, Jun Nagai, Riho Kurata, Kenji Shimizu, Xiaofeng Cui, Takayuki Isagawa, Hiroaki Semba, Jun Ishihara, Yasuhiro Yoshida, Norihiko Takeda, Koji Maemura, Tomo Yonezawa
    • Journal Title

      Marine Drugs

      Volume: 18 Issue: 3 Pages: 161-161

    • DOI

      10.3390/md18030161

    • NAID

      120006988256

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Establishment of novel cells stably secreting various human IL-18 recombinant proteins.2019

    • Author(s)
      Asuka Kumagai, Kenji Shimizu, Riho Kurata, Xiaofeng Cui, Takayuki Isagawa, Msamitsu Harada, Jun Nagai, Yasuhiro Yoshida, Kei-ichi Ozaki, Norihiko Takeda, Hiroaki Semba and Tomo Yonezawa
    • Journal Title

      Current Pharmaceutical Biotechnology

      Volume: 20 Issue: 1 Pages: 47-55

    • DOI

      10.2174/1389201020666190206203640

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 原虫感染症における生体内を検出するアッセイ系の樹立2020

    • Author(s)
      米沢 朋
    • Organizer
      第43回日本分子生物学会年会、ワークショップ(環境因子と生体防御機構をイメージする!)
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 大気汚染物質を評価するための分泌型アルカリフォスファターゼを用いたリポーター細胞の樹立2020

    • Author(s)
      米澤 朋、倉田 里穂、熊谷 飛鳥、尾崎 惠一、吉田 安宏
    • Organizer
      第42回日本分子生物学会年会 環境因子と生体修復反応
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Establishment of novel cells stably secreting various human IL18 recombinant proteins.2018

    • Author(s)
      Asuka Kumagai, Kenji Shimizu, Riho Kurata, Xiaofeng Cui, Takayuki Isagawa, Masamitsu Harada, Jun Nagai,Yasuhiro Yoshida, Kei-ichi Ozaki and Tomo Yonezawa
    • Organizer
      ASCB/EMBO meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Establishment of novel reporter cells stably maintaining transcription factor-driven human secreted alkaline phosphatase expression.2018

    • Author(s)
      Asuka Kumagai, Riho Kurata, Xiaofeng Cui, Masamitsu Harada, Jun Nagai, Yasuhiro Yoshida, Kei-ichi Ozaki and Tomo Yonezawa
    • Organizer
      ASCB/EMBO meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 多様なヒト組み替えタンパク質を安定に分泌する新規細胞の樹立2018

    • Author(s)
      熊谷 飛鳥、清水 謙次、倉田 里穂、Xiaofeng Cui、砂河 孝行、原田 将光、永井 潤、吉田 安宏、尾﨑 惠一、米澤 朋
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] ヒト分泌型アルカリフォスファターゼ発現を安定に維持する新規リポーター細胞の樹立2018

    • Author(s)
      倉田 里穂、熊谷 飛鳥、Xiaofeng Cui、原田 将光、永井 潤、吉田 安宏、尾﨑 惠一、米澤 朋
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Book] 別冊Bio Clinica Vol. 9, No.1, ヒトIL-18特異的シグナルを検出する新規リポーター細胞の樹立および独自ライブラリーを用いた創薬への取り組み2020

    • Author(s)
      倉田 里穂, 原田 将光, 砂河 孝行、仙波 宏章、武田 憲彦、前村 浩二、米澤 朋
    • Publisher
      北陵館
    • Related Report
      2020 Annual Research Report
  • [Book] Medical Science Digest Vol. 46, No.10, 自己免疫疾患への治療薬作出のための新規リポーター細胞の樹立: 独自ライブラリーを用いた創薬への取り組2020

    • Author(s)
      倉田 里穂, 原田 将光,米澤 朋
    • Publisher
      ニューサイエンス社
    • Related Report
      2020 Annual Research Report
  • [Book] BIO Clinica 2019年 8月臨時増刊号 ヒトγδT細胞抗腫瘍活性を用いた新規免疫細胞治療のための創薬研究2019

    • Author(s)
      熊谷飛鳥, 倉田里穂, 尾崎惠一, 砂河孝行, 仙波宏章, 武田憲彦, 前村浩二, 米澤朋
    • Total Pages
      100
    • Publisher
      北隆館
    • Related Report
      2019 Research-status Report
  • [Book] アレルギーの臨床 2019年9月臨時増刊号 新規ベーチェット病感受性遺伝子TRIM39RおよびⅠ型IFN応答2019

    • Author(s)
      倉田 里穂、米澤 朋、尾崎 惠一、猪子 英俊
    • Total Pages
      90
    • Publisher
      北隆館
    • Related Report
      2019 Research-status Report
  • [Book] BIO Clinica 2019年 5月号 多発性硬化症等の自己免疫疾患治療薬作出のための化合物スクリーニング2019

    • Author(s)
      倉田 里穂、熊谷 飛鳥、尾崎 惠一、米澤 朋
    • Total Pages
      106
    • Publisher
      北陵館
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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