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2012 Fiscal Year Final Research Report

Development of anti-cancer agents targeting the endocytic pathway

Research Project

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Project/Area Number 22681034
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Living organism molecular science
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

KAWATANI Makoto  独立行政法人理化学研究所, 化合物ライブラリー評価研究チーム, 専任研究員 (50391925)

Research Collaborator MUROI Makoto  独立行政法人理化学研究所, 化合物ライブラリー評価研究チーム, 専任研究員 (30261168)
FUTAMURA Yushi  独立行政法人理化学研究所, 化学情報・化合物創製チーム, 協力研究員 (70525857)
KAZAMI Sayaka  独立行政法人理化学研究所, 化合物ライブラリー評価研究チーム, 協力技術員
HONDA Kaori  独立行政法人理化学研究所, 化合物ライブラリー評価研究チーム, 協力技術員
Project Period (FY) 2010 – 2012
Keywords癌 / 小分子化合物 / エンドサイトーシス
Research Abstract

The purpose of this study is to construct a cell morphology-based high-content screening system and to develop anti-cancer agents targeting the endocytic pathway. We constructed a chemical-genetic phenotype profiling system based on the high-content cell morphology database, Morphobase. We showed that NPD1801, which perturbs the endocytic pathway, targeted calmodulin, caused the activation of Ras-Raf pathway, the inhibition of the fusion of late endosome and lysosome, and the dysfunction of lysosome, and resulted in the cancer cell death.

  • Research Products

    (27 results)

All 2013 2012 2011 2010 Other

All Journal Article (14 results) Presentation (12 results) Book (1 results)

  • [Journal Article] Dual structure-activity relationship of osteoclastogenesis inhibitor methyl gerfelin based on TEG scanning.2013

    • Author(s)
      Kanoh N., Suzuki T., Kawatani M., Katou Y., Oshima Y., Osada H., and Iwabuchi Y.
    • Journal Title

      Bioconjug. Chem.

      Volume: 24 Pages: 44-52

  • [Journal Article] Morphobase, an encyclopedic cell morphology database, and its use for drug target identification.2012

    • Author(s)
      Futamura Y., Kawatani M., Kazami S., Tanaka K., Muroi M., Shimizu T., Tomita K., Watanabe N., and Osada H.
    • Journal Title

      Chem. Biol.

      Volume: 19 Pages: 1620-1630

  • [Journal Article] Violaceols function as actin inhibitors inducing cell shape elongation in fibroblast cells.2012

    • Author(s)
      Asami Y., Jang J.-H., Oh H., Sohn J. H., Kim J. W., Moon D. O., Kwon O., Kawatani M., Osada H., Kim B. Y., and Ahn J. S.
    • Journal Title

      Biosci. Biotechnol. Biochem.

      Volume: 76 Pages: 1431-1437

  • [Journal Article] Effect of reveromycin A on experimental tooth movement in OPG-/- mice.2012

    • Author(s)
      Tanaka M., Miyazawa K., Tabuchi M., Yabumoto T., Kadota M., Yoshizako M., Yamane C., Kawatani M., Osada H., Maeda H., and Goto S.
    • Journal Title

      J. Dent. Res.

      Volume: 91 Pages: 771-776

  • [Journal Article] Protein disulfide isomerase-mediated disulfide bonds regulate the gelatinolytic activity and secretion of matrix metalloproteinase-9.2012

    • Author(s)
      Khan M. M., Simizu S., Suzuki T., Masuda, A., Kawatani M., Muroi M., Dohmae N., and Osada H.
    • Journal Title

      Exp. Cell Res.

      Volume: 318 Pages: 904-914

  • [Journal Article] Spirotoamides A and B, novel 6,6-spiroacetal polyketides isolated from a microbial metabolite fraction library.2012

    • Author(s)
      Nogawa T., Takahashi S., Okano A., Kawatani M., Uramoto M., Saito T., and Osada H.
    • Journal Title

      J. Antibiot.

      Volume: 65 Pages: 123-128

  • [Journal Article] The potential of protein disulfide isomerase as a therapeutic drug target.2012

    • Author(s)
      Khan M. M., Simizu S., Kawatani M., and Osada H.
    • Journal Title

      Oncol. Res.

      Volume: 19 Pages: 445-453

  • [Journal Article] Identification of a small-molecule inhibitor of DNA topoisomerase II by proteomic profiling.2011

    • Author(s)
      Kawatani M., Takayama H., Muroi M., Kimura S., Maekawa T., and Osada H.
    • Journal Title

      Chem. Biol.

      Volume: 18 Pages: 743-751

  • [Journal Article] Genetic safeguard against mycotoxin cyclopiazonic acid production in Aspergillus oryzae.2011

    • Author(s)
      Kato N., Tokuoka M., Shinohara Y., Kawatani M., Uramoto M., Seshime Y., Fujii I., Kitamoto K., Takahashi T., Takahashi S., Koyama Y., and Osada, H.
    • Journal Title

      Chembiochem

      Volume: 12 Pages: 1376-1382

  • [Journal Article] Discovery of a small molecule PDI inhibitor that inhibits reduction of HIV-1 envelope glycoprotein gp120.2011

    • Author(s)
      Khan M. M., Simizu S., Lai N. S., Kawatani M., Shimizu T., and Osada H.
    • Journal Title

      ACS Chem. Biol.

      Volume: 6 Pages: 245-251

  • [Journal Article] Application of proteomic profiling based on 2D-DIGE for classification of compounds according to the mechanism of action.2010

    • Author(s)
      Muroi M., Kazami S., Noda K., Kondo H., Takayama H., Kawatani M., Usui T., and Osada H.
    • Journal Title

      Chem. Biol.

      Volume: 17 Pages: 460-470

  • [Journal Article] Glyoxalase-I is a novel target against Bcr-Abl+ leukemic cells acquiring stem-like characteristics in hypoxic environment.2010

    • Author(s)
      Takeuchi M., Kimura S., Kuroda J., Ashihara E., Kawatani M., Osada H., Umezawa K., Yasui E., Imoto M., Tsuruo T., Yokota A., Tanaka R., Nagao R., Nakahata T., Fujiyama Y., and Maekawa T.
    • Journal Title

      Cell Death Diff.

      Volume: 17 Pages: 1211-1220

  • [Journal Article] Isolation of new polyketide metabolites, linearolides A and B, from a Streptomyces sp. RK95-74.

    • Author(s)
      Ueki M., Koshiro N., Aono H., Kawatani M., Uramoto M., Kawasaki H., and Osada H.
    • Journal Title

      J. Antibiot.

      Volume: (in press)

  • [Journal Article] Creation of novel reveromycin derivatives by alcohol added fermentation.

    • Author(s)
      Nogawa T., Takahashi S., Sekiyama Y., Takagi H., Uramoto M., Koshino H., Kawatani M., Shimizu T., and Osada H.
    • Journal Title

      J. Antibiot.

      Volume: (in press)

  • [Presentation] Proteome- and cell morphology-based target identification for RKB3564F070, a new cytotoxic fungal metabolite2012

    • Author(s)
      Makoto Kawatani, Harumi Aono, Toshihiko Nogawa, Makoto Muroi, Yushi Futamura, and Hiroyuki Osada
    • Organizer
      The 1st official conference of the international chemical biology society
    • Place of Presentation
      Boston, USA
    • Year and Date
      20121004-05
  • [Presentation] Chemical biology studies on inhibitors of cancer bone metastases2012

    • Author(s)
      川谷誠
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      20120919-21
  • [Presentation] Identification of a molecular target for RKB3564F070, a new cytotoxic fungal metabolite2012

    • Author(s)
      川谷誠、青野晴美、室井誠、二村友史、長田裕之
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      20120919-21
  • [Presentation] Identification of novel tubulin polymerization inhibitors by proteomic profiling2012

    • Author(s)
      Makoto Kawatani, Makoto Muroi, and Hiroyuki Osada
    • Organizer
      The 16th JFCR-ISCC
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      20120125-26
  • [Presentation] 破骨細胞を標的とする小分子化合物の化学遺伝学的解析2012

    • Author(s)
      川谷誠、長田裕之
    • Organizer
      第153回日本獣医学会学術集会
    • Place of Presentation
      大宮
    • Year and Date
      2012-03-27
  • [Presentation] Identification of novel tubulin polymerization inhibitors by proteomic profiling2011

    • Author(s)
      Makoto Kawatani, Kouji Tomita, Makoto Muroi, Sayaka Kazami, Harumi Aono, Takeshi Shimizu, and Hiroyuki Osada
    • Organizer
      AACR-NCI-EORTC International Conference "Molecular Targets and Cancer Therapeutics"
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      20111112-16
  • [Presentation] プロテオームプロファイリングによるチューブリン重合阻害剤の同定2011

    • Author(s)
      川谷誠、青野晴美、室井誠、長田裕之
    • Organizer
      第70回日本癌学会学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      20111003-05
  • [Presentation] プロテオームプロファイリングによるチューブリン重合阻害剤の同定2011

    • Author(s)
      川谷誠、富田康司、風見紗弥香、青野晴美、室井誠、清水猛、長田裕之
    • Organizer
      第15回日本がん分子標的治療学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      20110622-24
  • [Presentation] Antitumor activity of NPD723, a novel potent cell differentiation-inducing agent in leukemic cells2010

    • Author(s)
      Makoto Kawatani, Harumi Aono, and Hiroyuki Osada
    • Organizer
      22nd AACR-NCI-EORTC International Conference "Molecular Targets and Cancer Therapeutics"
    • Place of Presentation
      Berlin, Germany
    • Year and Date
      20101116-19
  • [Presentation] The identification of a novel inhibitor of osteoclastogenesis that acts via inhibition of glyoxalase I2010

    • Author(s)
      Makoto Kawatani, and Hiroyuki Osada
    • Organizer
      2010 RIKEN Chemical Biology International Symposium
    • Place of Presentation
      Saitama, Japan
    • Year and Date
      20101026-27
  • [Presentation] 細胞質空胞化を誘導するNPD1801 の作用機作解析2010

    • Author(s)
      川谷誠、青野晴美、早川洋一、長田裕之
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      20100922-24
  • [Presentation] 細胞質空胞化を誘導するNPD1801 の作用機構解析2010

    • Author(s)
      川谷誠、風見紗弥香、青野晴美、早川洋一、長田裕之
    • Organizer
      第14回日本がん分子標的治療学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      20100706-08
  • [Book] 「細胞骨格系」日本臨床(増刊号)2012

    • Author(s)
      川谷誠、長田裕之
    • Total Pages
      130-134

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Published: 2014-08-29  

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