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Studies on screening for bioactive compounds targeting gene repair, recombination and splicing systems.

Research Project

Project/Area Number 20380070
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bioproduction chemistry/Bioorganic chemistry
Research InstitutionNational Institute of Advanced Industrial Science and Technology

Principal Investigator

SHINYA Kazuo  National Institute of Advanced Industrial Science and Technology, バイオメディシナル情報研究センター, 主任研究員 (20251481)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2010: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2009: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2008: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Keywords遺伝子修復 / 遺伝子組み換え / スプライシング / 抗がん剤 / 天然物 / スクリーニング / スプラシング阻害 / p27癌抑制遺伝子 / 抗腫瘍物質 / マクロライド系化合物 / 発がんプロモーター / 代謝拮抗剤 / マイトトキシン / スプライソソーム / 天然化合物 / 相同組み換え
Research Abstract

One of the significant problems about the cancer chemotherapy is the acquisition of resistance to antitumor agents against cancer cells, in which the gene repair mechanisms takes part in. Thus, gene repair system is considered to be the promising molecular target for the development of anti-tumor agents. In addition to repair system, transcription and modification such as splicing system is also shown to be attractive target for cancer chemotherapy.
In this research, we succeeded to construct the good assay systems to monitor gene repair and splicing activities, and also succeeded to discover inhibitors against these activities from natural products including microbial secondary metabolites as the results of wide drug screenings.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (40 results)

All 2010 2009 2008

All Journal Article (29 results) (of which Peer Reviewed: 29 results) Presentation (11 results)

  • [Journal Article] New xanthoquinodin-like compounds, JBIR-97, -98 and -99, obtained from marine sponge-derived fungus Tritirachium sp.SpB081112MEf2.2010

    • Author(s)
      Jun-ya Ueda, Motoki Takagi, Kazuo Shin-ya
    • Journal Title

      J.Antibiot. 63(10)

      Pages: 615-618

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A new angucycline and a new butenolide isolated from lichen-derived Streptomyces spp.2010

    • Author(s)
      Keiichiro Motohashi, Motoki Takagi, Hideki Yamamura, Masayuki Hayakawa, Kazuo Shin-ya.
    • Journal Title

      J.Antibiot. 63(9)

      Pages: 545-548

    • NAID

      10030710013

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] JBIR-69, a new peptide metabolite from Streptomyces sp.OG05.2010

    • Author(s)
      Takeshi Fujiwara, Aya Nagai, Motoki Takagi, Kazuo Shin-ya.
    • Journal Title

      J.Antibiot. 63(2)

      Pages: 95-96

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anti-influenza virus compound from Streptomyces sp.RI18.2010

    • Author(s)
      M.Takagi, K.Motohashi, A.Nagai, M.Izumikawa, M.Tanaka, S.Fuse, T.Doi, K.Iwase, A.Kawaguchi, K.Nagata, T.Takahashi, K.Shin-ya
    • Journal Title

      Org.Lett.

      Volume: 12(20) Pages: 4664-4666

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A new angucycline and a new butenolide isolated from lichen-derived Streptomyces spp.2010

    • Author(s)
      K.Motohashi, M.Takagi, H.Yamamura, M.Hayakawa, K.Shin-ya
    • Journal Title

      J.Antibiot.

      Volume: 63(9) Pages: 545-548

    • NAID

      10030710013

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] JBIR-97, -98 and -99, obtained from marine sponge-derived fungus Tritirachium sp.SpB081112MEf2.2010

    • Author(s)
      J.Ueda, M.Takagi, K.Shin-ya
    • Journal Title

      J.Antibiot.

      Volume: 63(10) Pages: 627-629

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] JBIR-69, a new peptide metabolite from Streptomyces sp.OG05.2010

    • Author(s)
      Takeshi Fujiwara, Aya Nagai, Motoki Takagi, Kazuo Shin-ya
    • Journal Title

      J.Antibiot. 63

      Pages: 95-96

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] JBIR-52, a novel antimycin-like compound, from Streptomyces sp.ML55.2009

    • Author(s)
      Ikuko Kozone, Jun-ya Ueda, Motoki Takagi, Kazuo Shin-ya.
    • Journal Title

      J.Antibiot. 62(10)

      Pages: 593-595

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] JBIR-44, a new bromotyrosine compound from a marine sponge Psammaplysilla purpurea.2009

    • Author(s)
      Takeshi Fujiwara, Ji-Hwan Hwang, Akihiko Kanamoto, Hiroshi Nagai, Motoki Takagi, Kazuo Shin-ya.
    • Journal Title

      J.Antibiot. 62(7)

      Pages: 393-395

    • NAID

      10030635826

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] JBIR-17, a novel trichostatin analogue from Streptomyces sp.26634.2009

    • Author(s)
      Jun-ya Ueda, Ji-Hwan Hwang, Taira Kato, Atsushi Ochiai, Kunio Isshiki, Motoki Takagi, Kazuo Shin-ya.
    • Journal Title

      J.Antibiot. 62(5)

      Pages: 283-285

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] New glycosylated derivatives of versipelostatin, the GRP78/Bipmolecular chaperone down-regulator, from Streptomyces versipellis 4083-SVS6.2009

    • Author(s)
      Ping Zhao, Jun-ya Ueda, Ikuko Kozone, Shuhei Chijiwa, Motoki Takagi,Fumitaka Kudo, Makoto Nishiyama, Kazuo Shin-ya, Tomohisa Kuzuyama.
    • Journal Title

      Org.Biomol.Chem. 7(7)

      Pages: 144-1460

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] JBIR-23 and -24, novel anticancer agents from Streptomyces sp. AK-AB27.2009

    • Author(s)
      Keiichiro Motohashi, Ji-Hwan Hwang, Motoki Takagi, Kazuo Shin-ya.
    • Journal Title

      Org.Lett. 11(2)

      Pages: 285-288

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Preventing the unfolded protein response via aberrant activation of 4E-binding protein 1 by versipelostatin.2009

    • Author(s)
      Junichi Matsuo, Yoshinori Tsukumo, Junko Sakurai, Satomi Tsukahara, Hae-Ryong Park, Kazuo Shin-ya, Toshiki Watanabe, Takashi Tsuruo, Akihiro Tomida.
    • Journal Title

      Cancer Sci. 100(2)

      Pages: 327-333

    • NAID

      10025142654

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] JBIR-17, a novel trichostatin analogue from Streptomyces sp.266342009

    • Author(s)
      Jun-ya Ueda, Ji-Hwan Hwang, Taira Kato, Atsushi Ochiai, Kunio Isshiki, Motoki Takagi, Kazuo Shin-ya
    • Journal Title

      J.Antibiot. 62

      Pages: 283-285

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] JBIR-44, a new bromotyrosine compound from a marine sponge Psammaplysilla purpurea.2009

    • Author(s)
      Takeshi Fujiwara, Ji-Hwan Hwang, Akihiko Kanamoto, Hiroshi Nagai, Motoki Takagi, Kazuo Shin-ya
    • Journal Title

      J.Antibiot. 62

      Pages: 393-395

    • NAID

      10030635826

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] JBIR-52, a novel antimycin-like compound, from Streptomyces sp.ML552009

    • Author(s)
      Ikuko Kozone, Jun-ya Ueda, Motoki Takagi, Kazuo Shin-ya
    • Journal Title

      J.Antibiot. 62

      Pages: 593-595

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] JBIR-23 and -24, novel anticancer agents from Streptomyces sp. AK-AB272009

    • Author(s)
      K. Motohashi, J. -H. Hwang, M. Takagi, K Shin-ya
    • Journal Title

      Org. Lett. 11

      Pages: 285-288

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] New glycosylated derivatives of versipelostatin, the GRP78/Bip molecular chaperone down-regulator, from Streptomyces versipellis 4083-SVS62009

    • Author(s)
      P. Zhao, J. Ueda, I. Kozone, S. Chijiwa, M. Takagi, F. Kudo, M. Nishiyama, K. Shin-ya, T. Kuzuyama
    • Journal Title

      Org. Biomol. Chem. 7

      Pages: 1454-1460

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Macrocyclic hexaoxazoles as sequence-and mode-selective G-quadruplex binders.2008

    • Author(s)
      Masayuki. Tera, Hiromichi Ishizuka, Motoki Takagi, Masami Suganuma, Kazuo Shin-ya, Kazuo Nagasawa.
    • Journal Title

      Angew.Chem.Int.Ed. 47(30)

      Pages: 5557-5560

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] JBIR-26, a novel natural compound from Streptomyces sp. AK-AH76, regulates mammalian circadian clock.2008

    • Author(s)
      Miho Izumikawa, Hideki Ukai, Motoki Takagi, Hiroki R. Ueda, Kazuo Shin-ya.
    • Journal Title

      J.Antibiot. 61(12)

      Pages: 756-758

    • NAID

      10024825110

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel versipelostatin analogue, versipelostatin F isolated from Streptomyces versipellis 4083-SVS6.2008

    • Author(s)
      Jun-ya Ueda, Shuhei Chijiwa, Motoki Takagi, Kazuo Shin-ya.
    • Journal Title

      J.Antibiot. 61(12)

      Pages: 752-755

    • NAID

      10024825100

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel versipelostatin analogue, versipelostatin F isolated from Streptomyces versipellis 4083-SVS62008

    • Author(s)
      J. Ueda, S. Chijiwa, M. Takagi, K. Shin-ya
    • Journal Title

      J. Antibiot 61

      Pages: 725-755

    • NAID

      10024825100

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] JBIR-26, a novel natural compound from Streptomyces sp. AK-AH76, regulates mammalian circadian clock2008

    • Author(s)
      M. Izumikawa, H. Ukai, M. Takagi, H. Ueda, K. Shin-ya
    • Journal Title

      J. Antibiot 61

      Pages: 326-329

    • NAID

      10024825110

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FANCJ helicase defective in Fanconia anemia and breast cancer unwinds G-quadruplex DNA to defend genomic stability2008

    • Author(s)
      Y. Wu, K. Shin-ya, R. M. Brosh, Jr.
    • Journal Title

      Mol. Cell Biol. 28

      Pages: 4116-4128

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Macrocyclic hexaoxazoles as sequence- and mode-selective G-quadruplex binders2008

    • Author(s)
      M. Tera, H. Ishizuka, M. Takagi, M. Suganuma, K. Shin-ya, K. Nagasawa
    • Journal Title

      Angew. Chem. Int. Ed 47

      Pages: 5557-5560

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efrapeptin J, a new down-regulator of the molecular chaperone GRP78 from a marine Tolypocladium sp.2008

    • Author(s)
      Y. Hayakawa, Y. Hattori, T. Kawasaki, K. Kanoh, K. Adachi, Y. Shizuri, K. Shin-ya
    • Journal Title

      J. Antibiot. 28

      Pages: 365-371

    • NAID

      10021927947

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Studying telomere replication by Q-CO-FISH : the effect of telomestatin, a potent G-quadruplex ligand2008

    • Author(s)
      N. Arnoult, K. Shin-ya, J. -A. Londono-Vallejo
    • Journal Title

      Cytogenet. Genome Res. 122

      Pages: 229-236

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of TLS DNA polymerases eta and kappa in processing naturally occurring structured DNA in human cells.2008

    • Author(s)
      R. Betous, N. Puget, J. Selves, D. S. Biard, K. Shin-ya, K. M. Vasquez, C. Cazaux, J. -S. Hoffmann, et al.
    • Journal Title

      Mol. Carcinog. 48

      Pages: 369-378

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preventing the unfolded protein response via aberrant activation of 4E-binding protein 1 by versipelostatin2008

    • Author(s)
      J. Matsuo, Y. Tsukumo, J. Sakurai, S. Tsukahara, H. -R. Park, K. Shin-ya, T. Watanabe, T. Tsuruo, A. Tomida
    • Journal Title

      Cancer Sci. 100

      Pages: 327-333

    • NAID

      10025142654

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 海綿由来の放線菌より単離した新規anthracycline2010

    • Author(s)
      本橋慶一郎、高木基樹、新家一男
    • Organizer
      2010年日本農芸化学会総会
    • Place of Presentation
      東京
    • Year and Date
      2010-03-28
    • Related Report
      2010 Final Research Report
  • [Presentation] プロテアソーム形成を阻害する化合物JBIR-22に関する研究2010

    • Author(s)
      泉川美穂、橋本絢子、広川貴次、杉本聡、加藤平、高木基樹、新家一男
    • Organizer
      2010年日本農芸化学会総会
    • Place of Presentation
      東京
    • Year and Date
      2010-03-28
    • Related Report
      2010 Final Research Report
  • [Presentation] 新規GRP78発現抑制物質JBIR-52に関する研究2010

    • Author(s)
      小曽根郁子、上田純也、高木基樹、新家一男
    • Organizer
      2010年日本農芸化学会総会
    • Place of Presentation
      東京
    • Year and Date
      2010-03-28
    • Related Report
      2010 Final Research Report
  • [Presentation] JBIR-23, a novel compound of microbial origin, induces cytotoxicity against malignant mesothelioma cells by tubulin polymerization and apoptosis2010

    • Author(s)
      新家一男、村上秀樹、Hwang Ji-Hwan、関戸好孝、高木基樹
    • Organizer
      8th AACR-JCA Joint meeting
    • Place of Presentation
      Waikoloa, Hawaii
    • Year and Date
      2010-02-09
    • Related Report
      2010 Final Research Report
  • [Presentation] JBIR-23, a novel compound of microbial origin, induces cytotoxicity against malignant mesothelioma cells by tubulin polymerization and apoptosis2010

    • Author(s)
      高木基樹、村上秀樹、Hwang Ji-Hwan、関戸好孝、新家一男
    • Organizer
      AACR Cell Death Mechanisms and Cancer Therapy
    • Place of Presentation
      San Diego
    • Year and Date
      2010-02-03
    • Related Report
      2010 Final Research Report
  • [Presentation] 新種のStreptomyces属から単離された新規化合物に関する研究2009

    • Author(s)
      本橋慶一郎、Tabrez Shams Khan、小牧久幸、小曽根育子、向井啓、高木基樹、新家一男
    • Organizer
      天然有機化合物討論会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-10-08
    • Related Report
      2010 Final Research Report
  • [Presentation] 新規化合物JBIR-23の中皮腫細胞に対する殺細胞活性発現メカニズムに関する報告2009

    • Author(s)
      Hwang Ji-Hwan、本橋慶一郎、関戸好孝、高木基樹、新家一男
    • Organizer
      2009年日本農芸化学会総会
    • Place of Presentation
      福岡
    • Year and Date
      2009-03-28
    • Related Report
      2010 Final Research Report
  • [Presentation] 中皮腫細胞に対して抗がん活性を示す化合物のスクリーニング2009

    • Author(s)
      本橋慶一郎、Hwang Ji-Hwan、関戸好孝、高木基樹、新家一男
    • Organizer
      2009年日本農芸化学会総会
    • Place of Presentation
      福岡
    • Year and Date
      2009-03-28
    • Related Report
      2010 Final Research Report
  • [Presentation] 中皮腫細胞に対して抗癌活性を示す化合物のスクリーニング2009

    • Author(s)
      本橋慶一郎, J. -H. Hwang, 関戸好孝, 高木基樹, 新家一男
    • Organizer
      日本農芸化学会2009年度大会
    • Place of Presentation
      福岡
    • Year and Date
      2009-03-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] 新規化合物JBIR-23の中皮腫細胞に対する殺細胞活性発現メカニズムに関する報告2009

    • Author(s)
      J. -H. Hwang, 本橋慶一郎, 関戸好孝, 高木基樹, 新家一男
    • Organizer
      日本農芸化学会2009年度大会
    • Place of Presentation
      福岡
    • Year and Date
      2009-03-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] 新規抗酸化化合物JBIR-12に関する研究2009

    • Author(s)
      泉川美穂, 永井文, 土井隆行, 高木基樹, 新家一男
    • Organizer
      日本農芸化学会2009年度大会
    • Place of Presentation
      福岡
    • Year and Date
      2009-03-28
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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