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Mechanistic analysis for anti-RANKL antibody drug associated severe adverse reactions

Research Project

Project/Area Number 26670265
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Applied pharmacology
Research InstitutionThe University of Tokyo

Principal Investigator

Kariya Yoshiaki  東京大学, 医学部附属病院, 助教 (20633168)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsシステム薬理学 / 毒性予測 / 分子標的薬 / 毒性予測法 / 医薬品副作用
Outline of Final Research Achievements

Denosumab, an anti-RANKL antibody drug, has been clinically used in recent years. However, it has been suspected that Denosumab has a potential to cause severe hypocalcemia. Since drug adverse reactions (ADR) often occur under the mechanisms which are not expected at development, there are difficulties in revealing such mechanisms in many cases. Overcoming these difficulties leads to mechanism based ADR management, resulting in safer drug therapy. Therefore, in this research, we have established a method to obtain the clues for ADR mechanisms based on systems-pharmacological techniques. With this method, we approached the mechanism behind Denosumab inducing hypocalcemia.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (5 results)

All 2016 2015

All Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Book (1 results)

  • [Presentation] Prediction method of cardiotoxicity triggered by kinase inhibition2016

    • Author(s)
      Yoshiaki Kariya
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] Prediction of TKI Associated Cardiotoxicity Based on Network Analyses of Intracellular Signaling Pathways2015

    • Author(s)
      Yoshiaki Kariya
    • Organizer
      Workshop on Pharmacological Mechanism-Based Drug Safety Prediction
    • Place of Presentation
      FDA, Silver Spring, MD, US
    • Year and Date
      2015-08-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 細胞内シグナルネットワークを考慮したシステム薬理学的心毒性予測2015

    • Author(s)
      苅谷嘉顕、本間雅、鈴木洋史
    • Organizer
      第88回 日本薬理学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-03-19
    • Related Report
      2014 Research-status Report
  • [Presentation] Prediction of cardiac cell apoptosis using systems pharmacological methodologies2015

    • Author(s)
      Yoshiaki Kariya, Masashi Honma, Keita Tokuda, Hiroshi Suzuki
    • Organizer
      新学術領域研究「多階層生体機能学」終了記念シンポジウム
    • Place of Presentation
      大阪
    • Year and Date
      2015-03-04 – 2015-03-06
    • Related Report
      2014 Research-status Report
  • [Book] Systems Pharmacology and Pharmacodynamics Chapter 16, Systems Pharmacology of Tyrosine Kinase Inhibitor-Associated Toxicities2016

    • Author(s)
      Hiroshi Suzuki, Yoshiaki Kariya, Masashi Honma
    • Publisher
      Springer
    • Related Report
      2015 Annual Research Report

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Published: 2014-04-04   Modified: 2017-05-10  

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