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Effects of IL-17 on intervertebral disc degeneration and the investigation of the new small-molecule IL-17 inhibitor for treating degenerative discs

Research Project

Project/Area Number 17K10946
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionTokai University

Principal Investigator

SUYAMA Kaori  東海大学, 医学部, 准教授 (20433914)

Co-Investigator(Kenkyū-buntansha) 酒井 大輔  東海大学, 医学部, 准教授 (10408007)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsインターロイキン17 / 低分子化合物 / インシリコ創薬 / 椎間板 / IL-17 / 椎間板変性 / 創薬
Outline of Final Research Achievements

IL-17A is a member of the IL-17 cytokine family, which mediates the induction of some inflammatory cytokines and chemokines. We evaluated the effects of IL-17A on nucleus pulposus (NP) cells and pharmacotherapeutic potential of the new small-molecule inhibitors that blockIL-17A receptor binding.
We analyzed the spatial structure of the protein-protein interactions between IL-17A and IL-17A receptor (IL-17RA), and identified four small-molecule inhibitors that accessed the IL-17A-binding site of IL-17RA, as determined by in silico analysis of numerous drug molecules. Our results showed that IL-17A promoted the expression of the factors which lead degeneration of intervertebral discs (IVD); however, the four small-molecule inhibitors suppressed augmentation of IVD degeneration factors. These results showed that IL-17A regulated the factors which mediate disc degeneration and the small-molecule inhibitor of IL-17A could be useful for pharmacotherapy of intervertebral disc disease.

Academic Significance and Societal Importance of the Research Achievements

本研究は椎間板におけるIL-17Aの作用解析から薬物を使用した治療標的としての可能性までを包括した体系的研究である。既存のIL-17阻害剤は生物学的製剤が主体であり、副作用として重篤な感染症や高い薬価、投与法が注射薬に限定される点、等が問題とされている。これに対し低分子化合物の利点としては、生物学的製剤より安価であり、水溶性に優れるため外用薬、経口薬としての投与が可能となる等が挙げられる。現在、椎間板変性以外にも多くの疾患に対してIL-17Aの関与が報告されており、上述した低分子阻害剤化合物の利点はこれらの椎間板疾患を含めたIL-17関連疾患に対する新しい治療薬としての応用も期待できる。

Report

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

    (11 results)

All 2019 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (7 results) (of which Int'l Joint Research: 2 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 2 results)

  • [Journal Article] Effects of interleukin-17A in nucleus pulposus cells and its small-molecule inhibitors for intervertebral disc disease.2018

    • Author(s)
      Kaori Suyama, Daisuke Sakai, Noriaki Hirayama, Yoshihiko Nakamura, Erika Matsushita, Hayato Terayama, Ning Qu, Osamu Tanaka, Kou Sakabe, Masahiko Watanabe
    • Journal Title

      Journal of Cellular and Molecular Medicine

      Volume: Nov;22 Issue: 11 Pages: 5539-5551

    • DOI

      10.1111/jcmm.13828

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 新規低分子IL-17A阻害剤による椎間板変性治療法の可能性を評価する2019

    • Author(s)
      隅山香織
    • Organizer
      第48回 日本脊椎脊髄病学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] In Silico創薬による新規低分子IL-17A阻害剤を用いた椎間板変性治療の可能性2019

    • Author(s)
      隅山香織
    • Organizer
      第34回 日本整形外科学会基礎学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] The potential utility of interleukin-17A inhibitors for the intervertebral disc disease treatment2019

    • Author(s)
      Kaori Suyama
    • Organizer
      Orthopaedic Research Society 2019 Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新規低分子IL-17A阻害剤を用いた椎間板変性治療法の評価2019

    • Author(s)
      隅山香織
    • Organizer
      第32回日本軟骨代謝学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 椎間板変性に対する新規低分子化合物を用いたIL-17A阻害療法の評価2018

    • Author(s)
      隅山香織
    • Organizer
      第33回日本整形外科学会基礎学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Effects of interleukin-17A on intervertebral disc degeneration: Interleukin-17A can be a potential therapeutic target for treating degenerative discs2018

    • Author(s)
      Kaori Suyama
    • Organizer
      Orthopaedic Research Society 2018 Annual Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 椎間板変性に対するIL-17の作用2017

    • Author(s)
      隅山香織
    • Organizer
      第32回日本整形外科学会基礎学術集会
    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] IL-17A活性阻害剤およびその用途2019

    • Inventor(s)
      酒井大輔、平山令 明、隅山香織
    • Industrial Property Rights Holder
      酒井大輔、平山令 明、隅山香織
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Acquisition Date
      2019
    • Related Report
      2019 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] IL-17A活性阻害剤およびその用途2019

    • Inventor(s)
      酒井大輔、平山令明、隅山香織
    • Industrial Property Rights Holder
      酒井大輔、平山令明、隅山香織
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2018 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] IL-17A活性阻害剤およびその用途2018

    • Inventor(s)
      酒井大輔、平山令明、隅山香織
    • Industrial Property Rights Holder
      酒井大輔、平山令明、隅山香織
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2017 Research-status Report

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

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