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Development of anticancer drug targeting choline transporter by drug repositioning

Research Project

Project/Area Number 17K08315
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pharmacology in pharmacy
Research InstitutionTokyo Medical University

Principal Investigator

Inazu Masato  東京医科大学, 医学部, 教授 (00297269)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsコリン / トランスポーター / がん治療 / choline / transporter / cancer / ceramide / survivin / apoptosis / 癌 / ドラッグリポジショニング / 薬理学
Outline of Final Research Achievements

A novel choline transporter-like protein 1 (CTL1) was found to be highly expressed in cancer cells, and its inhibition induced apoptosis and suppressed cell growth. Furthermore, the search for CTL1 inhibitors from existing pharmaceutical and plant-derived organic compound libraries led to the discovery of promising isoquinoline derivatives. This hit compound may be a candidate for a new molecularly targeted cancer drug with a novel therapeutic mechanism.

Academic Significance and Societal Importance of the Research Achievements

本研究は、これまでの抗がん剤が標的としていない新規のがん治療標的分子であるcholine transporter-like protein 1 (CTL1)を見出し、このCTL1を阻害しアポトーシスによる細胞死を誘導する化合物を発見した。本ヒット化合物のメカニズムも明らかにし、癌細胞移植ヌードマウスにて抗腫瘍効果を確認した。本研究における成果は、新たな分子標的治療薬の開発に繋がり、予防・治療医学および創薬科学への発展に貢献するものである。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (25 results)

All 2020 2019 2018 2017

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (15 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Functional Expression of Choline Transporter-Like Protein 1 in LNCaP Prostate Cancer Cells: A Novel Molecular Target2020

    • Author(s)
      Saiki I, Yara M, Yamanaka T, Uchino H, Inazu M
    • Journal Title

      Biomolecules & Therapeutics

      Volume: 28 Issue: 2 Pages: 195-201

    • DOI

      10.4062/biomolther.2019.097

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protein kinase C promotes choline transporter like protein 1 function via improved cell surface expression in immortalized human hepatic cells.2020

    • Author(s)
      Ishikawa T, Suwanai H, Shikuma J, Suzuki R, Yamanaka T, Odawara M, Inazu M
    • Journal Title

      Mol Med Rep

      Volume: 21 Pages: 777-785

    • DOI

      10.3892/mmr.2019.10894

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of new therapeutic drugs for pancreatic cancer targeting choline transporter-like protein 1 (CTL1/SLC44A1)2020

    • Author(s)
      Inazu M, Hirai K, Watanabe S, Nishijima N, Shibata K, Hase A, Gido R, Yamanaka T
    • Journal Title

      Annals of Oncology

      Volume: 31 Pages: S8-S9

    • DOI

      10.1016/j.annonc.2020.01.044

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional Expression of Choline Transporters in the Blood-Brain Barrier2019

    • Author(s)
      Inazu M
    • Journal Title

      Nutrients

      Volume: 11 Issue: 10 Pages: 2265-2265

    • DOI

      10.3390/nu11102265

    • NAID

      40021215533

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exploratory research in plant-derived natural organic compounds with antitumor activity targeting choline transporter2019

    • Author(s)
      Inazu M, Hirai K, Watanabe S, Shibata K, Nishijima N, Yamanaka T
    • Journal Title

      Proceedings for Annual Meeting of The Japanese Pharmacological Society

      Volume: 92 Issue: 0 Pages: 3-P-111

    • DOI

      10.1254/jpssuppl.92.0_3-P-111

    • NAID

      130007813290

    • ISSN
      2435-4953
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Choline transporter-like protein 1 (CTL1/SLC44A1) is a therapeutic target molecule for prostate cancer therapy2019

    • Author(s)
      Masato Inazu, Iwao Saiki, Hiroyuki Uchino, Tsuyoshi Yamanaka
    • Journal Title

      Annals of Oncology

      Volume: 30 Pages: i7-i7

    • DOI

      10.1093/annonc/mdz029.011

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular and Functional Characterization of Choline Transporter-Like Proteins in Esophageal Cancer Cells and Potential Therapeutic Targets.2017

    • Author(s)
      Fumiaki Nagashima, Ryohta Nishiyama, Beniko Iwao, Yuiko Kawai, Chikanao Ishii, Tsuyoshi Yamanaka, Hiroyuki Uchino and Masato Inazu
    • Journal Title

      Biomolecules & Therapeutics

      Volume: 26 Issue: 4 Pages: 1-10

    • DOI

      10.4062/biomolther.2017.113

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 癌治療の新しい分子標的としての choline transporter-like proteins(CTLs)2017

    • Author(s)
      稲津正人
    • Journal Title

      東京医科大学雑誌

      Volume: 75 Pages: 51-65

    • NAID

      40021215508

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Choline transporter-like protein 1 (CTL1/SLC44A1) is a therapeutic target molecule for cancer therapy2019

    • Author(s)
      Hirai K, Nishijima N, Shibata K, Watanabe S, Yamanaka T, Inazu M
    • Organizer
      The 7th China-Japan Joint Meeting of Basic and Clinical Pharmacology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] がん治療標的分子としてのCholine transporter-like proteins (CTLs/SLC44A)~植物由来天然化合物からの探索研究~2019

    • Author(s)
      渡邊才一郎、平井花歩、西島希、長谷紅音、儀同りこ、山中力、稲津正人
    • Organizer
      第14回トランスポーター研究会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Drug discovery from plant-derived natural products as a treatment against pancreatic cancer: Search for choline transporter inhibitors2019

    • Author(s)
      平井花歩、渡邊才一郎、柴田薫、西島希、山中力、稲津正人
    • Organizer
      第8回医薬工3大学包括連携推進シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] 植物化学とがん治療の融合 ~コリン代謝系を標的とした抗腫瘍活性を有する植物由来天然有機化合物の探索~2019

    • Author(s)
      渡邊才一郎、林睦実、西島希、柴田薫、吉森彩、町田優一、松井元介、森井貫、平井花歩、山中力、稲津正人
    • Organizer
      第8回医薬工3大学包括連携推進シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] がん治療におけるcholine transporter-like protein 1 (CTL1)を標的とした新規化合物の抗腫瘍効果2019

    • Author(s)
      平井花歩、渡邊才一郎、西島希、柴田薫、長谷紅音、儀同りこ、山中力、稲津正人
    • Organizer
      第4回黒潮カンファレンス
    • Related Report
      2019 Annual Research Report
  • [Presentation] ヒト肝がん細胞株HuH-7におけるコリントランスポーターの機能解析およびコリン取り込み阻害剤の効果2019

    • Author(s)
      長谷紅音、儀同りこ、平井花歩、渡邊才一郎、山中力、稲津正人
    • Organizer
      第184回 東京医科大学医学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Choline transporter-like protein 1 (CTL1/SLC44A1) is a therapeutic target molecule for prostate cancer therapy2019

    • Author(s)
      Masato Inazu, Iwao Saiki, Hiroyuki Uchino, Tsuyoshi Yamanaka
    • Organizer
      TAT2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Exploratory research for plant-derived natural organic compounds with anti-tumor activity targeting choline transporter2019

    • Author(s)
      Masato Inazu, Kaho Hirai, Saiichiro Watanabe, Kaoru Shibata, Nozomi Nishijima, Tsuyoshi Yamanaka
    • Organizer
      The 92th Annual Meeting of the Japanese Pharmacological Society
    • Related Report
      2018 Research-status Report
  • [Presentation] Functional analysis of choline transporter-like proteins in rheumatoid arthritis synovial fibroblasts: A novel molecular target for rheumatoid arthritis2018

    • Author(s)
      Masato Inazu, Masayuki Seki, Tsuyoshi Yamanaka, Masato Odawara
    • Organizer
      The 18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 植物化学とがん治療の融合 ~コリントランスポーターを標的とした舌がん治療剤の探索~2018

    • Author(s)
      柴田薫、西島希、渡邊才一郎、吉森彩、石川卓也、松井元介、森井貫、近津大地、稲津正人
    • Organizer
      第13回トランスポーター研究会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 植物化学とがん治療の融合 ~Fight Against Glioma~2018

    • Author(s)
      西島希、柴田薫、渡邊才一郎、吉森彩、石川卓也、町田優一、林睦実、山中力、稲津正人
    • Organizer
      第13回トランスポーター研究会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] コリントランスポーターを標的とした抗腫瘍活性を有する植物由来天然有機化合物の探索2018

    • Author(s)
      稲津正人、柴田薫、西島希、渡邊才一郎、平井花歩、山中力
    • Organizer
      第7回 医薬工3大学包括連携推進シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] 植物化学とがん治療の融合~コリン代謝系を標的とした抗腫瘍活性を有する植物由来天然有機化合物の探索~2018

    • Author(s)
      渡邊才一郎、林睦実、西島希、柴田薫、吉森彩、町田優一、松井元介、森井貫、平井花歩、山中力、稲津正人
    • Organizer
      第182回東京医科大学医学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Functional expression of choline transporter-like proteins (CTLs/SLC44A) in human tongue cancer: A novel molecular target for tongue cancer therapy.2017

    • Author(s)
      Masato Inazu
    • Organizer
      10th BioMedical Transporters Conference
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 細胞増殖と生存に対するコリントランスポーターCTLs/SLC44A の役割2017

    • Author(s)
      稲津正人
    • Organizer
      第59回歯科基礎医学会学術大会アップデートシンポジウム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Book] 新スタンダード栄養・食物シリーズ13、分子栄養学―科学的根拠に基づく食理学―2019

    • Author(s)
      稲津正人(分担)
    • Total Pages
      256
    • Publisher
      東京科学同人
    • ISBN
      9784807916733
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] がん治療剤2020

    • Inventor(s)
      稲津正人
    • Industrial Property Rights Holder
      稲津正人
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-053259
    • Filing Date
      2020
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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