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Development and mechanistic study of novel anti- Alzheimer's disease drugs with PKC-ε selective activation

Research Project

Project/Area Number 22790120
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Drug development chemistry
Research InstitutionHyogo University of Health Sciences

Principal Investigator

SHIMIZU Tadashi  兵庫医療大学, 薬学部, 助教 (40509022)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Keywords医薬品化学 / PKC-ε / 認知症治療剤 / DCP-LA / 構造活性相関 / ターゲット探索 / PKC-e / 認知症治療 / 生理活性脂肪酸 / 光学分割
Research Abstract

We have already synthetic route for the preparation of all of the four isomers of enantiomerically pure DCP-LA employing lipase-mediated resolution method, and found the most active stereoisomers. However, first synthetic route was difficult for gram-scale synthesis of optically active DCP-LA. In this research, we have developed synthetic route for gram-scale preparation of all of the four isomers of enantiomerically pure DCP-LA, and found the most active stereoisomers in vivo system. In addition, we found that novel free fatty acid derivative HUHS2002 activated α7 ACh receptor responces. Fuethemore, we identified some candidates of target protein of DCP-LA with affinity chromatography methods.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (24 results)

All 2013 2012 2011 2010

All Journal Article (22 results) (of which Peer Reviewed: 22 results) Presentation (2 results)

  • [Journal Article] Effects of Newly Synthesized DCP-LA-Phospholipids on Protein Kinase C and Protein Phosphatases.2013

    • Author(s)
      T. Kanno, A. Tsuchiya, T.Shimizu, S. Nakao, A. Tanaka, T. Nishizaki
    • Journal Title

      Cell.Physiol. Biochem.

      Volume: 31 Pages: 555-564

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of GluA1 AMPA Receptor throughPKC Phosphorylation Induced by Free Fatty Acid Derivative HUHS2002.2013

    • Author(s)
      T. Nishimoto, T. Kanno, T. Shimizu, A. Tanaka, T. Nishizaki
    • Journal Title

      Lipids

      Volume: 43 Pages: 23-28

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of GluA1 AMPA Receptor through PKC Phosphorylation Induced by Free Fatty Acid Derivative HUHS2002.2013

    • Author(s)
      Takaaki Nishimoto
    • Journal Title

      Lipids

      Volume: 48 Issue: 1 Pages: 23-28

    • DOI

      10.1007/s11745-012-3736-4

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Indomethacin Serves as a Potential Inhibitor ofProtein Phosphatases.2012

    • Author(s)
      T. Kanno, A. Tsuchiya, T. Shimizu, A. Tanaka, T. Nishizaki
    • Journal Title

      Cell. Physiol. Biochem.

      Volume: 30 Pages: 1014-1022

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Novel Indomethacin Action: Selective and DirectActivation of Protein Kinase C-ε2012

    • Author(s)
      T. Kanno, A. Tsuchiya, T. Shimizu, A. Tanaka, T. Nishizaki
    • Journal Title

      Cell. Physiol. Biochem.

      Volume: 30 Pages: 771-777

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Free Fatty Acid Derivative HUHS2002Potentiates α7 ACh Receptor Responces Through Indirect Activation of CaMKII.2012

    • Author(s)
      T. Kanno, T. Shimizu, A. Tanaka, T. Nishimoto, T. Nishizaki
    • Journal Title

      Lipids

      Volume: 49 Pages: 865-871

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 8-[2-(2-Pentyl-Cyclopropylmethyl)-Cyclopropyl]-Octanoic Acid and Its DIastereomers Improve Age-Related Cognitive Deteriotation.2012

    • Author(s)
      T. Kanno, T. Yaguchi, T. Shimizu, A. Tanaka, T. Nishizaki
    • Journal Title

      Lipids

      Volume: 47 Pages: 687-695

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthetic Route to Optically Pure NorcantharidinAnalog NCA-01, a Highly Selective Protein Phosphatase 2B inhibitor, and Its Derivatives.2012

    • Author(s)
      T. Shimizu, M. Iizuka, H. Matsukura, D. Hashizume, M. Sodeoka
    • Journal Title

      Chem. Asian J.

      Volume: 7 Pages: 1221-1230

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Indomethacin Enhances Learning and Memory Potential by Interacting with CaMKII.2012

    • Author(s)
      T. Kanno, T. Yaguchi, T. Nagata, T. Shimizu, A. Tanaka, T. Nishizaki
    • Journal Title

      J. Cell Physiol.

      Volume: 227 Pages: 919-926

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 8-[2-(2-Pentyl-Cyclopropylmethyl)-Cyclopropyl]-Octanoic Acid and Its Diastereomers Improve Age-Related Cognitive Deteriotation.2012

    • Author(s)
      Takeshi Kanno
    • Journal Title

      Lipids

      Volume: 47 Issue: 7 Pages: 687-695

    • DOI

      10.1007/s11745-012-3677-y

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Free Fatty Acid Derivative HUHS2002 Potentiates a7 ACh Receptor Responces Through Indirect Activation of CaMKII.2012

    • Author(s)
      Takeshi Kanno
    • Journal Title

      Lipids

      Volume: 47 Issue: 9 Pages: 865-871

    • DOI

      10.1007/s11745-012-3701-2

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel Indomethacin Action: Selective and Direct Activation of Protein Kinase C-e2012

    • Author(s)
      Takeshi Kanno
    • Journal Title

      Cell. Physiol. Biochem.

      Volume: 30 Issue: 3 Pages: 771-777

    • DOI

      10.1159/000341456

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Indomethacin Serves as a Potential Inhibitor of Protein Phosphatases.2012

    • Author(s)
      Takeshi Kanno
    • Journal Title

      Cell. Physiol. Biochem.

      Volume: 30 Issue: 4 Pages: 1014-1022

    • DOI

      10.1159/000341478

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Indomethacin Enhances Learning and Memory Potential by Interacting with CaM KII2012

    • Author(s)
      Takaeshi Kannno
    • Journal Title

      Journal of Cellular Physiology

      Volume: 227 Issue: 3 Pages: 917-916

    • DOI

      10.1002/jcp.22800

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthetic Route to Optically Pure Norcantharidin Analog NCA-01, a Highly Selective Protein Phosphatase 2B inhibitor, and Its Derivatives2012

    • Author(s)
      Tadashi Shimizu
    • Journal Title

      Chemistry-An Asian Journal

      Volume: (Published online) Issue: 6 Pages: 1221-1230

    • DOI

      10.1002/asia.201200077

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] α, β-DCP-LA Selectivity Activates PKC-ε andStimulates Neurotransmitter Release with the Highest Potency among 4 Diastereomers.2011

    • Author(s)
      T. Shimizu, T. Kanno, A. Tanaka, T. Nishizaki
    • Journal Title

      Cell. Physiol. Biochem.

      Volume: 27 Pages: 149-158

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Formal [6+4] cycloaddition of a dicobaltacetylene complex with furan derivatives.2011

    • Author(s)
      K. Dota, T. Shimizu, S. Hasegawa, M. Miyashia, K. Tanino
    • Journal Title

      Tetrahedron Lett.

      Volume: 52 Pages: 910-912

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] α,β-DCP-LA Selectivity Activates PKC-ε and Stimulates Neurotransmitter Release with the Highest Potency among 4 Diastereomers2011

    • Author(s)
      Tadashi Shimizu
    • Journal Title

      Cellular Physiology and Biochemistry

      Volume: 27 Pages: 149-158

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selective elution of target protein from affinityresins by a simple reductant with a thiol group.2010

    • Author(s)
      M. Mabuchi, M. Haramura, T. Shimizu, T. Nishizaki, A. Tanaka
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: 20 Pages: 7361-7364

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Total synthesis of furanether B. Construction of a hydroazulene skeleton via a novel [5 + 2] cycloaddition reaction of silyloxyallene.2010

    • Author(s)
      K. Mitachi, T. Yamamoto, F. Kondo, T. Shimizu, M. Miyashita, K. Tanino
    • Journal Title

      Chem. Lett.

      Volume: 39 Pages: 630-632

    • NAID

      10027181753

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cyclooctanone synthesis via a formal [6+2] cycloaddition reaction of a dicobalt acetylene complex.2010

    • Author(s)
      K. Mitachi, T. Shimizu, M. Miyashita, K. Tanino
    • Journal Title

      Teterahedron Lett.

      Volume: 51 Pages: 3983-3986

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Selective elution of target protein from affinity resins by a simple reductant with a thiol group2010

    • Author(s)
      Miyuki Mabuchi
    • Journal Title

      Bioorganic Medicinal Chemistry Letters

      Volume: 20 Pages: 7361-7364

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Synthesis and Evaluation of optically active DCP-LA as a PKC-ε selective activator (Oral presentation).2011

    • Author(s)
      T. Shimizu, M. Mabuchi, T. Kanno,T. Nishizaki, A. Tanaka
    • Organizer
      8th AFMC International Medicinal Chemistry Symposium
    • Place of Presentation
      Tokyo
    • Year and Date
      2011-12-01
    • Related Report
      2012 Final Research Report
  • [Presentation] Synthesis and Evaluation of optically active DCP-LA as a PKC-ε selective activator2011

    • Author(s)
      Tadashi Shimizu
    • Organizer
      8th AFMC Internatonal Medicinal Chemistry Symposium
    • Place of Presentation
      東京
    • Year and Date
      2011-12-01
    • Related Report
      2011 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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