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Creation of novel molecular-targeted anticancer drugs focused on specific phenotypic changes of cells in tumor

Research Project

Project/Area Number 26242074
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomolecular chemistry
Research InstitutionOsaka University

Principal Investigator

KOBAYASHI Motomasa  大阪大学, 薬学研究科, 招へい教授 (40116033)

Co-Investigator(Kenkyū-buntansha) 荒井 雅吉  大阪大学, 薬学研究科, 特任教授(常勤) (80311231)
古徳 直之  大阪大学, 薬学研究科, 助教 (20362618)
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥43,680,000 (Direct Cost: ¥33,600,000、Indirect Cost: ¥10,080,000)
Fiscal Year 2017: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2016: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2015: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2014: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Keywords抗がん剤 / がん微小環境 / 標的分子 / 海洋生物 / 分子標的治療薬 / 分子標的治療
Outline of Final Research Achievements

In this study, we focused on metabolic or phenotypic changes of cells in tumor microenvironments and searched for marine natural products capable of regulating them. Then, 10 bioactive natural products including 7 novel compounds were discovered. In addition, total synthesis of isolated bioactive natural products, study of structure- activity relationship by synthesized analog compounds, and evaluation of in vivo efficacy were carried out. Furthermore, for the purpose of exploring new drug targets, we analyzed the action-mechanisms and target molecule of bioactive natural products. As a result, the action-mechanism or target molecule of 5 compounds were clarified.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (45 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (3 results) Journal Article (13 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 12 results,  Acknowledgement Compliant: 10 results,  Open Access: 2 results) Presentation (26 results) (of which Int'l Joint Research: 5 results,  Invited: 9 results) Book (1 results) Remarks (2 results)

  • [Int'l Joint Research] ランプン大学(インドネシア)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Lampung University(インドネシア)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Lampung University(インドネシア)

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Marine spongean polybrominated diphenyl ethers, selective growth inhibitors against the cancer cells adapted to glucose starvation, inhibits mitochondrial complex II2017

    • Author(s)
      Arai Masayoshi、Shin Dayoung、Kamiya Kentaro、Ishida Ryosuke、Setiawan Andi、Kotoku Naoyuki、Kobayashi Motomasa
    • Journal Title

      Journal of Natural Medicines

      Volume: 71 Issue: 1 Pages: 44-49

    • DOI

      10.1007/s11418-016-1025-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Biakamides A-D, Unique Polyketides from a Marine Sponge, Act as Selective Growth Inhibitors of Tumor Cells Adapted to Nutrient Starvation2017

    • Author(s)
      Naoyuki Kotoku, Ryosuke Ishida, Hirokazu Matsumoto, Masayoshi Arai, Kazunari Toda, Andi Setiawan, Osamu Muraoka, and Motomasa Kobayashi
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 82 Issue: 3 Pages: 1705-1718

    • DOI

      10.1021/acs.joc.6b02948

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 低酸素環境で機能する海洋天然物2017

    • Author(s)
      荒井雅吉
    • Journal Title

      細胞

      Volume: 50 Pages: 38-41

    • NAID

      40021807802

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Exploring New Drug Targets through the Identification of Target Molecules of Bioactive Natural Products2016

    • Author(s)
      Masayoshi Arai
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 136 Issue: 4 Pages: 669-676

    • DOI

      10.1248/yakushi.15-00281

    • NAID

      130005140773

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2016-04-01
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Furospinosulin-1, marine spongean furanosesterterpene, suppresses the growth of hypoxia-adapted cancer cells by binding to transcriptional regulators p54nrb and LEDGF/p75.2016

    • Author(s)
      Arai, M.; Kawachi, T.; Kotoku, N.; Nakata, C.; Kamada, H.; Tsunoda, S.; Tsutsumi, Y.; Endo, H.; Inoue, M.; Sato, H.; Kobayashi, M.
    • Journal Title

      ChemBioChem

      Volume: 17 Issue: 2 Pages: 181-189

    • DOI

      10.1002/cbic.201500519

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] <i>N</i>-Methylniphatyne A, a New 3-Alkylpyridine Alkaloid as an Inhibitor of the Cancer Cells Adapted to Nutrient Starvation, from an Indonesian Marine Sponge of <i>Xestospongia</i> sp.2016

    • Author(s)
      M. Arai, K. Kamiya, D. Shin, H. Matsumoto, T. Hisa, A. Setiawan, N. Kotoku, M. Kobayashi
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 64 Issue: 7 Pages: 766-771

    • DOI

      10.1248/cpb.c16-00118

    • NAID

      130005160059

    • ISSN
      0009-2363, 1347-5223
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Search for Anti-angiogenic Substances from Natural Sources2016

    • Author(s)
      Kotoku, N.; Arai, M.; Kobayashi, M.
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 64 Issue: 2 Pages: 128-134

    • DOI

      10.1248/cpb.c15-00744

    • NAID

      130005121723

    • ISSN
      0009-2363, 1347-5223
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Enantioselective synthesis of dictyoceratin-A (smenospondiol) and -C, hypoxia-selective growth inhibitors from marine sponge2015

    • Author(s)
      Yuji Sumii, Naoyuki Kotoku, Akinori Fukuda, Takashi Kawachi, Yuta Sumii, Masayoshi Arai, Motomasa Kobayashi
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 23 Issue: 5 Pages: 966-975

    • DOI

      10.1016/j.bmc.2015.01.021

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure-activity relationship and in vivo anti-tumor evaluation of dictyoceratin-A and -C, hypoxia-selective growth inhibitors from marine sponge.2015

    • Author(s)
      Sumii, Y.; Kotoku, N.; Fukuda, A.; Kawachi, T.; Sumii, Y.; Arai, M.; Kobayashi, M.
    • Journal Title

      Marine Drugs

      Volume: 13 Issue: 12 Pages: 7419-7432

    • DOI

      10.3390/md13127074

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Anti-dormant mycobacterial activity and target analysis of nybomycin produced by a marine-derived Streptomyces sp.2015

    • Author(s)
      Arai, M.; Kamiya, K.; Pruksakorn, P.; Sumii, Y.; Kotoku, N.; Joubert, J.-P.; Moodley, P.; Han, C.; Shin, D.; Kobayashi, M.
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 23 Issue: 13 Pages: 3534-3541

    • DOI

      10.1016/j.bmc.2015.04.033

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Xylarianaphthol-1, a novel dinaphthofuran derivative, activates p21 promoter in a p53-independent manner.2014

    • Author(s)
      N. Kotoku, K. Higashimoto, M. Kurioka, M. Arai, A. Fukuda, Y. Sumii, Y. Sowa, T. Sakai, M. Kobayashi
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: 24 Issue: 15 Pages: 3389-3391

    • DOI

      10.1016/j.bmcl.2014.05.083

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Marine spongian sesquiterpene phenols, dictyoceratin-C and smenospondiol, display hypoxia-selective growth inhibition against cancer cells.2014

    • Author(s)
      M. Arai, T. Kawachi, H. Sato, A. Setiawan, M. Kobayashi
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: 24 Issue: 14 Pages: 3155-3157

    • DOI

      10.1016/j.bmcl.2014.04.116

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Synthesis and evaluation of effective photoaffinity probe molecule of furospinosulin-1, a hypoxia-selective growth Inhibitor.2014

    • Author(s)
      N. Kotoku, C. Nakata, T. Kawachi, T. Sato, X.H. Guo, A. Ito, Y. Sumii, M. Arai, M. Kobayashi
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 22 Issue: 7 Pages: 2102-2112

    • DOI

      10.1016/j.bmc.2014.02.026

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 海綿由来ブロモフェノール類のグルコース飢餓環境選択的増殖阻害活性と作用メカニズム解析2017

    • Author(s)
      古徳直之,申多英,石田良典,松本紘和,久智也,戸田和成,荒井雅吉,小林資正
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター等(宮城県仙台市)
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] 新規海洋天然物biakamide類の栄養飢餓環境選択的がん細胞増殖阻害活性とその作用メカニズム2017

    • Author(s)
      石田良典, 古徳直之, 荒井雅吉
    • Organizer
      第21回日本がん分子標的治療学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 海洋天然物の魅力と創薬研究への応用2017

    • Author(s)
      荒井雅吉
    • Organizer
      第40回 新適塾 「未来創薬への誘い」
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Structure-activity relationship and mechanistic analysis of biakamides, selective growth inhibitors against cancer cells under nutrient-starved conditions2017

    • Author(s)
      Ryosuke Ishida, Naoyuki Kotoku, Hirokazu Matsumoto, Sayaka Ichii, Motomasa Kobayashi, Masayoshi Arai
    • Organizer
      10th Seoul-Kyoto-Osaka Joint Symposium on Pharmaceutical Sciences For Young Scientists
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Exploring new medicinal seeds and drug targets from marine resources.2017

    • Author(s)
      Masayoshi Arai
    • Organizer
      JOINT SYMPOSIUM OF OSAKA UNIVERSITY WITH HIGHER EDUCATIONAL INSTITUTIONS OF BRUNEI DARUSSALAM
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] EXPLORING NEW DRUG TARGET BASED ON CHEMICAL BIOLOGY OF MARINE NATURAL PRODUCTS2016

    • Author(s)
      Masayoshi Arai
    • Organizer
      The 8th US-Japan Symposium on Marine Natural Products
    • Place of Presentation
      ホノルル(米国)
    • Year and Date
      2016-11-14
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 栄養飢餓環境選択的がん細胞増殖阻害物質biakamide類の構造活性相関と作用メカニズム解析2016

    • Author(s)
      石田良典,古徳直之,松本紘和,荒井雅吉,小林資正
    • Organizer
      第21回天然薬物の開発と応用シンポジウム
    • Place of Presentation
      千葉大学薬学部(千葉県千葉市)
    • Year and Date
      2016-10-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] 海洋天然物で切拓く新規薬剤標的分子2016

    • Author(s)
      荒井雅吉
    • Organizer
      第21回天然薬物の開発と応用シンポジウム
    • Place of Presentation
      千葉大学薬学部(千葉県千葉市)
    • Year and Date
      2016-10-27
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 低酸素環境選択的がん細胞増殖阻害物質dictyoceratin類の標的分子解析2016

    • Author(s)
      古徳直之,荒井雅吉,河内崇志,住井裕司,福田昭典,田中駿,小林資正
    • Organizer
      第58回天然有機化合物討論会
    • Place of Presentation
      東北大学百周年記念会館(宮城県仙台市)
    • Year and Date
      2016-09-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] 海洋生物由来の栄養飢餓選択的増殖阻害物質の探索と創薬への展開2016

    • Author(s)
      古徳直之
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 低栄養選択的がん細胞増殖阻害物質N-methylniphatyne Aの全合成2016

    • Author(s)
      古徳直之,松本紘和,久智也,申多英,山口亞由太,荒井雅吉,小林資正
    • Organizer
      第66回日本薬学会近畿支部総会・大会
    • Place of Presentation
      大阪薬科大学(大阪府高槻市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Synthetic study and target analysis of dictyoceratin-A and -C, hypoxia-selective growth inhibitors from marine sponge2015

    • Author(s)
      Naoyuki Kotoku, Yuji Sumii, Takashi Kawachi, Akinori Fukuda, Masayoshi Arai and Motomasa Kobayashi
    • Organizer
      PACIFICHEM 2015
    • Place of Presentation
      ホノルル(米国)
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] グルコース飢餓環境選択的がん細胞増殖阻害活性を有するポリケチドbiakamide類の全合成と構造活性相関2015

    • Author(s)
      石田良典,古徳直之,松本紘和,荒井雅吉,小林資正
    • Organizer
      第41回反応と合成の進歩シンポジウム
    • Place of Presentation
      近畿大学(大阪府東大阪市)
    • Year and Date
      2015-11-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] 栄養飢餓環境選択的がん細胞増殖阻害物質の探索2015

    • Author(s)
      荒井雅吉,申多英,松本紘和,神谷謙太朗,久智也,古徳直之,小林資正
    • Organizer
      日本生薬学会第62年会
    • Place of Presentation
      長良川国際会議場(岐阜県岐阜市)
    • Year and Date
      2015-09-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] 底生海洋生物成分からの医薬シーズの探索研究2015

    • Author(s)
      小林資正
    • Organizer
      第50回天然物化学談話会
    • Place of Presentation
      グリーンピア岩沼 モンタナリゾート(宮城県岩沼市)
    • Year and Date
      2015-07-01
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 低酸素環境選択的がん細胞増殖阻害物質dictyoceratin-Cの標的分子解析2015

    • Author(s)
      河内崇志,荒井雅吉,古徳直之,小林資正
    • Organizer
      第19回日本がん分子標的治療学会学術集会
    • Place of Presentation
      松山全日空ホテル(愛媛県松山市)
    • Year and Date
      2015-06-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] Phenotypic screeningによる活性天然物探索と新規薬剤標的の開拓2015

    • Author(s)
      荒井雅吉
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸学院大学(神戸)
    • Year and Date
      2015-03-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Cortistatin Aアナログ化合物の構造活性相関と標的同定への応用2015

    • Author(s)
      古徳直之、伊藤 葵、◯水野華奈子、渋谷俊一、小林資正
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      デザイン・クリエイティブセンター神戸(神戸)
    • Year and Date
      2015-03-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 活性天然物の標的分子解析による新規薬剤標的の探索2015

    • Author(s)
      荒井雅吉
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸学院大学(神戸)
    • Year and Date
      2015-03-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 低栄養選択的増殖阻害物質fasciospyrinadinoneの全合成2015

    • Author(s)
      古徳直之,松本紘和,久智也,戸田和成,荒井雅吉,小林資正
    • Organizer
      第65回日本薬学会近畿支部総会・大会
    • Place of Presentation
      大阪大谷大学(大阪府富田林市)
    • Related Report
      2015 Annual Research Report
  • [Presentation] 腫瘍内細胞の表現型変化を制御する海洋天然物からの創薬とケミカルバイオロジー研究2014

    • Author(s)
      荒井雅吉
    • Organizer
      第32回メディシナルケミストリーシンポジウム
    • Place of Presentation
      神戸国際会議場(神戸)
    • Year and Date
      2014-11-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] グルコース飢餓環境選択的がん細胞増殖阻害作用を有する新規ポリケチド類の化学構造と生物活性2014

    • Author(s)
      ◯古徳直之,戸田和成,荒井雅吉,石田良典,松本紘和,村岡 修,小林資正
    • Organizer
      第56回天然有機化合物討論会
    • Place of Presentation
      高知県立県民文化ホール(高知)
    • Year and Date
      2014-10-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] 低酸素環境選択的細胞増殖阻害活性物質dictyoceratin-Cの合成研究2014

    • Author(s)
      住井裕司、古徳直之、◯福田昭典、河内崇志、角居雄太、荒井雅吉、小林資正
    • Organizer
      第64回日本薬学会近畿支部総会・大会
    • Place of Presentation
      京都薬科大学(京都)
    • Year and Date
      2014-10-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cortistatin A アナログ化合物の効率的合成法の開発2014

    • Author(s)
      古徳直之、◯渋谷俊一、竹島亜季、角居雄太、伊藤 葵、水野華奈子、小林資正
    • Organizer
      第64回日本薬学会近畿支部総会・大会
    • Place of Presentation
      京都薬科大学(京都)
    • Year and Date
      2014-10-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Phenotypic Screening and Chemical Biology for Exploring New Medicinal Seeds and Drug Targets2014

    • Author(s)
      Masayoshi Arai
    • Organizer
      The 8th JSP-CCTCNM-KSP Joint Symposium on Pharmacognosy
    • Place of Presentation
      福岡大学薬学部(福岡)
    • Year and Date
      2014-09-13
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 海洋天然物furospinosulin-1を利用する新規がん細胞低酸素適応因子の創出2014

    • Author(s)
      ◯河内崇志,荒井雅吉,古徳直之,小林資正
    • Organizer
      第18回日本がん分子標的治療学会学術集会
    • Place of Presentation
      TKPガーデンシティ仙台(仙台)
    • Year and Date
      2014-06-25
    • Related Report
      2014 Annual Research Report
  • [Book] アルカロイドの科学2017

    • Author(s)
      荒井雅吉, 小林資正
    • Total Pages
      534
    • Publisher
      化学同人
    • ISBN
      9784759814187
    • Related Report
      2017 Annual Research Report
  • [Remarks] 大阪大学大学院 薬学研究科 天然物化学分野ホームページ

    • URL

      http://www.phs.osaka-u.ac.jp/homepage/b012/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 大阪大学大学院 薬学研究科 天然物化学分野 ホームページ

    • URL

      http://www.phs.osaka-u.ac.jp/homepage/b012/

    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2019-03-29  

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