Development of anticancer platinum complexes that recognize a specific region of nucleic acid.

• Project/Area Number: 21750177
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Chemistry related to living body
• Research Institution: Suzuka University of Medical Science
• Principal Investigator: KOMEDA Seiji (2010) Suzuka University of Medical Science, 薬学部, 助教 (60425056); 米田 誠治 (2009) Suzuka University of Medical Science, 薬学部, 助教 (21750177)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 白金錯体 / 制がん剤 / X線結晶解析 / シスプラチン / DNA / X線結晶解

Research Abstract

We have synthesized a series of tetrazolate-bridged dinuclear Pt(II) complexes as a new class, in order to develop next-generation platinum-based anticancer drugs which are effective against cancers that are typically resistant to chemotherapy. In vivo antitumor efficacy of one of the complexes was evaluated on xenografted tumors of H460 non-small cell lung cancer and PANC-1 pancreatic cancer. The complex exhibited markedly high antitumor efficacy against pancreatic cancer. The tetrazolate-bridged complexes resulted to interact with DNA in a manner different from that of clinical platinum-based drugs.

Research Products

• [Journal Article] Unique platinum-DNA interactions may lead to more effective platinum-based antitumor drugs. (2011)
  • Author(s): Komeda, S.
  • Journal Title: Metallomics Epub ahead of print.
  • Peer Reviewed
• [Journal Article] A tetrazolato-bridged dinuclear platinum(II) complex exhibits markedly high in vivo antitumor activity against pancreatic cancer. (2011)
  • Author(s): Komeda, S., Lin, Y-L., Chikuma, M.
  • Journal Title: ChemMedChem 6 Pages: 987-990
  • Peer Reviewed
• [Journal Article] The phosphate clamp: a small and independent motif for nucleic acid backbone recognition. (2011)
  • Author(s): Komeda, S., Moulaei, T., Chikuma, M., Odani, A., Kipping, R., Farrell, N.P., Williams, L.D.
  • Journal Title: Nucleic Acids Res. 39 Pages: 325-336
  • Peer Reviewed
• [Journal Article] The phosphate clamp : a small and independent motif for nucleic acid backbone recognition. (2011)
  • Author(s): 米田誠治
  • Journal Title: Nucleic Acids Research Volume: 39 Pages: 325-36
  • Peer Reviewed
• [Journal Article] A tetrazolato-bridged dinuclear platinum(II)complex exhibits markedly high in vivo antitumor activity against pancreatic cancer. (2011)
  • Author(s): 米田誠治
  • Journal Title: ChemMedChem Volume: (Web公開)
  • Peer Reviewed
• [Journal Article] Unique platinum-DNA interactions may lead to more effective platinum-based antitumor drugs. (2011)
  • Author(s): 米田誠治
  • Journal Title: Metallomics Volume: (Web公開)
  • Peer Reviewed
• [Journal Article] 次世代白金制がん剤の創薬研究 (2010)
  • Author(s): 米田誠治
  • Journal Title: 日本化学会生体機能関連化学部会 NEWS LETTER 25 Pages: 7-10
• [Journal Article] A new class of rhodamine luminophores : design, syntheses and aggregation-induced emission enhancement. (2010)
  • Author(s): Kamino, S., Horio, Y., Komeda, S., Minoura, K., Ichikawa, H., Horigome, J., Tatsumi, A., Kaji, S., Yamaguchi, T., Usami, Y., Hirota, S., Enomoto, S., Fujita Y.
  • Journal Title: Chem.Commun. 46 Pages: 9013-9015
  • Peer Reviewed
• [Journal Article] Characteristic effect of an anticancer dinuclear platinum(II) complex on the higher-order structure of DNA. (2010)
  • Author(s): Kida, N., Katsuda, Y., Yoshikawa, Y., Komeda, S., Sato, T., Saito, Y., Chikuma, M., Suzuki, M., Imanaka, T., Yoshikawa, K.
  • Journal Title: J.Biol.Inorg.Chem. 15 Pages: 701-707
  • Peer Reviewed
• [Journal Article] Application of anomalous diffraction methods to the study of DNA and DNA-complexes. (2010)
  • Author(s): Watkins, D., Moulaei, T., Komeda, S., Williams, L.D.
  • Journal Title: Methods in Mol.Biol. 613 Pages: 133-152
• [Journal Article] 次世代白金制がん剤の創薬研究 (2010)
  • Author(s): 米田誠治
  • Journal Title: 社団法人日本化学会生体機能関連科学部会ニュースレター Volume: 25 Pages: 7-10
• [Journal Article] Application of anomalous diffraction methods to the study of DNA and DNA-complexes (2010)
  • Author(s): Derrick Watkins
  • Journal Title: Methods in Mol.Biol. 613 Pages: 133-152
  • Peer Reviewed
• [Journal Article] Characteristic effect of an anticancer dinuclear platinum(II)complex on the higher-order structure of DNA (2010)
  • Author(s): 木田直子
  • Journal Title: J.Biol.Inorg.Chem.
  • Peer Reviewed
• [Journal Article] Next-generation anticancer metallodrugs
  • Author(s): Komeda, S., Casini, A.
  • Journal Title: Cuur.Top.Med.Chem. in press
  • Peer Reviewed
• [Presentation] アゾラト架橋白金(II)二核錯体とDNAの相互作用様式に関する研究 (2011)
  • Author(s): 植村雅子, 藤澤豊, 飯田靖彦, 森井孫俊, 桜井弘, 千熊正彦, 米田誠治
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: コンペンションアーツセンター「グランシップ」(静岡市)
  • Year and Date: 2011-03-29
• [Presentation] In vivo 制がん活性を有する白金(II)複核錯体と核酸との相互作用様式 (2011)
  • Author(s): 米田誠治
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: コンペンションアーツセンター「グランシソプ」(静岡市)
  • Year and Date: 2011-03-26
• [Presentation] in vivo制がん活性を有する白金(II)複核錯体と核酸との相互作用様式 (2011)
  • Author(s): 米田誠治
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: コンベンションアーツセンター「グランシップ」(静岡県静岡市)
  • Year and Date: 2011-03-26
• [Presentation] DNA interactions of anticancer polynuclear Pt(II)complexes (2010)
  • Author(s): Komeda, S., Chikuma, M., Farrell, N.P., Williams, LD.
  • Organizer: 2010環太平洋国際化学会議
  • Place of Presentation: ハワイコンベンションセンター(米国ハワイ州ホノルル)
  • Year and Date: 2010-12-16
• [Presentation] DNA interactions of anticancer polynuclear Pt(II)complexes (2010)
  • Author(s): 米田誠治
  • Organizer: 2010環太平洋国際化学会議(PACIFICHEM 2010)
  • Place of Presentation: ハワイコンベンションセンター(米国ハワイ州ホノルル)
  • Year and Date: 2010-12-16
• [Presentation] 制がん活性を有するアゾラト架橋白金(II)二核錯体 (2010)
  • Author(s): 米田誠治, Yuh-ling Lin., 鈴木俊宏, 植村雅子, 千熊正彦
  • Organizer: 第2回メタロミクス研究フォーラム
  • Place of Presentation: 京都薬科大学(京都市)
  • Year and Date: 2010-11-30
• [Presentation] 制がん活性を有するアゾラト架橋白金(II)二核錯体 (2010)
  • Author(s): 米田誠治
  • Organizer: 第2回メタロミクス研究フォーラム
  • Place of Presentation: 京都薬科大学(京都市山科区)
  • Year and Date: 2010-11-03
• [Presentation] 制がん活性を有する白金(II)複核錯体と核酸との相互作用 (2010)
  • Author(s): 米田誠治, Yuh-Ling Lin, 鈴木俊宏, 植村雅子, Nicholas P.Farrell, Loren D.Williams, 小谷明, 千熊正彦
  • Organizer: 第4回バイオ関連化学シンポジウム
  • Place of Presentation: 大阪大学豊中キャンパス(大阪府豊中市)
  • Year and Date: 2010-09-25
• [Presentation] Interactions of anpcancer-active tetrazolato-bridged dinuclear pladnum(II) complexes with a nucleobase. (2010)
  • Author(s): 植村雅子, 藤澤豊, 飯田靖彦, 森井孫俊, 櫻井弘, 千熊正彦, 米田誠治
  • Organizer: 第20回金属の関与する生体関連反応シンポジウム
  • Place of Presentation: 徳島文理大学薬学部(徳島市)
  • Year and Date: 2010-06-25
• [Presentation] トリアゾール配位子を有する陽電荷白金二核錯体がDNAの高次構造に与える影響 (2010)
  • Author(s): 木田直子, 勝田陽介, 吉川祐子, 米田誠治, 佐藤卓史, 斉藤睦弘, 千熊正彦, 鈴木麻里, 今中忠行, 吉川研一
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 桃太郎アリーナ(岡山市)
  • Year and Date: 2010-03-29
• [Presentation] 制がん活性を有するテトラゾレート架橋 白金(II)二核錯体の核酸塩基との相互作用様式に関する研究 (2010)
  • Author(s): 植村雅子, 藤澤豊, 飯田靖彦, 森井孫俊, 桜井弘, 千熊正彦, 米田誠治
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 桃太郎アリーナ(岡山)
  • Year and Date: 2010-03-29
• [Presentation] 次世代白金制がん剤の開発研究 (2009)
  • Author(s): 米田誠治
  • Organizer: 大阪薬科大学ハイテクリサーチセンター平成21年度公開シンポジウム
  • Place of Presentation: 大阪薬科大学(大阪府高槻市)
  • Year and Date: 2009-12-05
• [Presentation] 次世代白金制がん剤の開発研究 (2009)
  • Author(s): 米田誠治
  • Organizer: 大阪薬科大学ハイテクリサーチセンター平成21年度公開シンポジウム
  • Place of Presentation: 大阪薬科大学(大阪府)
  • Year and Date: 2009-12-05
• [Presentation] 核酸の特定部位を認識する制がん白金錯体 (2009)
  • Author(s): 米田誠治, Nicholas P.Farrell, Loren D.Willialns, 小谷明, 千熊正彦
  • Organizer: 第24回生体機能関連化学部会シンポジウム
  • Place of Presentation: 九州大学医学部百周年会館(福岡市)
  • Year and Date: 2009-09-15
• [Presentation] 核酸の特定部位を認識する制がん白金錯体 (2009)
  • Author(s): 米田誠治
  • Organizer: 第24回生体機能関連化学部会シンポジウム
  • Place of Presentation: 九州大学医学部百周年会館(福岡県)
  • Year and Date: 2009-09-15
• [Presentation] X-ray crystallographic studies on DNA adduct formation by the anticancer-active polynuclear Pt(II)complexes (2009)
  • Author(s): Komeda, S., Odani, A., Chikuma, M., Farrell, N.P., Williams, L.D.
  • Organizer: The 2nd International Symposium on Biological Inorganic Chemistry ofthe New Era
  • Place of Presentation: 高山コンベンションセンター(岐阜県高山市)
  • Year and Date: 2009-07-31
• [Presentation] X-ray crystallographic studies on DNA adduct formation by the anticancer-active polynuclear Pt(II)complexes (2009)
  • Author(s): 米田誠治
  • Organizer: The 2nd International Symposium on Biological Inorganic Chemistry of the New Era
  • Place of Presentation: 高山コンベンションセンター(岐阜県)
  • Year and Date: 2009-07-31
• [Presentation] Design, structure-activity relationships and x-ray co-crystallography of anticancer-active polynyclear platinum(II) complexes (2009)
  • Author(s): Komeda, S., Odani, A., Chikuma, M., Farrell, N.P., Williams, L.D.
  • Organizer: 14th International Conference on Biological Inorganic Chemistry
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2009-07-27
• [Presentation] Design, structure-activity relationships and x-ray co-crystallography of anticancer-active polynyclear platinum(II)complexes (2009)
  • Author(s): 米田誠治
  • Organizer: 14th International Conference on Biological Inorganic Chemistry
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2009-07-27
• [Presentation] 制がん活性を有するカチオン性白金(II)複核錯体のDNAとの相互作用様式 (2009)
  • Author(s): 米田誠治, Nicholas P.Farrell, Loren D.Williams, 小谷明, 千熊正彦
  • Organizer: 第55回日本薬学会東海支部
  • Place of Presentation: 愛知学院大学薬学部(名古屋市)
  • Year and Date: 2009-07-11
• [Presentation] 制がん活性を有するカチオン性白金(II)複核錯体のDNAとの相互作用様式 (2009)
  • Author(s): 米田誠治
  • Organizer: 第55回日本薬学会東海支部
  • Place of Presentation: 愛知学院大学薬学部(愛知県)
  • Year and Date: 2009-07-11
• [Book] (2011)
  • Author(s): レアメタル便覧(共著)
  • Publisher: 丸善株式会社
• [Book] レアメタル便覧 (2011)
  • Author(s): 足立吟也
  • Total Pages: 1800
  • Publisher: 丸善株式会社
• [Book] (2010)
  • Author(s): 腫瘍薬学(共著)
  • Publisher: 南山堂
• [Book] 腫瘍薬学 (2010)
  • Author(s): 川西正祐
  • Total Pages: 573
  • Publisher: 南山堂
• [Remarks] ホームページ等
  • URL: http://www.suzuka-u.acjp/achievements/41-pp/ppkomeda.pdf
• [Remarks]
  • URL: http://www.suzuka-u.ac.jp/cgi-bin/teacher/view.cgi?no=171
• [Patent(Industrial Property Rights)] 白金錯体化合物およびその利用 (2010)
  • Inventor(s): 米田誠治,千熊正彦
  • Industrial Property Rights Holder: 天真堂製薬(株),(株)ヤクルト本社
  • Industrial Property Number: 2009-550001
  • Filing Date: 2010-07-12
• [Patent(Industrial Property Rights)] PLATINUM COMPLEX COMPOUND AND UTILIZATION OF THE SAME (2010)
  • Inventor(s): 米田誠治,千熊正彦
  • Industrial Property Rights Holder: 天真堂製薬(株),(株)ヤクルト本社
  • Filing Date: 2010-07-12
  • Overseas
• [Patent(Industrial Property Rights)] PLATINUM COMPLEX COMPOUND AND UTILIZATION OF THE SAME (2010)
  • Inventor(s): 米田誠治,千熊正彦
  • Industrial Property Rights Holder: 天真堂製薬(株),(株)ヤクルト本社
  • Filing Date: 2010-07-14
  • Overseas
• [Patent(Industrial Property Rights)] PLATINUM COMPLEX COMPOUND AND UTILIZATION OF THE SAME (2010)
  • Inventor(s): 米田誠治,千熊正彦
  • Industrial Property Rights Holder: 天真堂製薬(株),(株)ヤクルト本社
  • Filing Date: 2010-07-15
  • Overseas
• [Patent(Industrial Property Rights)] PLATINUM COMPLEX COMPOUND AND UTILIZATION OF THE SAME (2010)
  • Inventor(s): 米田誠治,千熊正彦
  • Industrial Property Rights Holder: 天真堂製薬(株),(株)ヤクルト本社
  • Filing Date: 2010-07-20
  • Overseas
• [Patent(Industrial Property Rights)] PLATINUM COMPLEX COMPOUND AND UTILIZATION OF THE SAME (2010)
  • Inventor(s): 米田誠治,千熊正彦
  • Industrial Property Rights Holder: 天真堂製薬(株),(株)ヤクルト本社
  • Filing Date: 2010-07-24
  • Overseas
• [Patent(Industrial Property Rights)] PLATINUM COMPLEX COMPOUND AND UTILIZATION OF THE SAME (2010)
  • Inventor(s): 米田誠治,千熊正彦
  • Industrial Property Rights Holder: 天真堂製薬(株),(株)ヤクルト本社
  • Filing Date: 2010-08-05
  • Overseas
• [Patent(Industrial Property Rights)] PLATINUM COMPLEX COMPOUND AND UTILIZATION OF THE SAME (2010)
  • Inventor(s): 米田誠治,千熊正彦
  • Industrial Property Rights Holder: 天真堂製薬(株),(株)ヤクルト本社
  • Filing Date: 2010-08-11
  • Overseas
• [Patent(Industrial Property Rights)] 白金錯体化合物およびその利用 (2010)
  • Inventor(s): 米田誠治, 千熊正彦
  • Industrial Property Rights Holder: 天真堂製薬(株), (株)ヤクルト本社
  • Industrial Property Number: 2009-550001
  • Filing Date: 2010-07-12
• [Patent(Industrial Property Rights)] PLATINUM COMPLEX COMPOUND AND UTILIZATION OF THE SAME (2010)
  • Inventor(s): 米田誠治, 千熊正彦
  • Industrial Property Rights Holder: 天真堂製薬(株), (株)ヤクルト本社
  • Filing Date: 2010-07-15
  • Overseas
• [Patent(Industrial Property Rights)] PLATINUM COMPLEX COMPOUND AND UTILIZATION OF THE SAME (2010)
  • Inventor(s): 米田誠治, 千熊正彦
  • Industrial Property Rights Holder: 天真堂製薬(株), (株)ヤクルト本社
  • Filing Date: 2010-07-12
  • Overseas
• [Patent(Industrial Property Rights)] PLATINUM COMPLEX COMPOUND AND UTILIZATION OF THE SAME (2010)
  • Inventor(s): 米田誠治, 千熊正彦
  • Industrial Property Rights Holder: 天真堂製薬(株), (株)ヤクルト本社
  • Filing Date: 2010-07-20
  • Overseas
• [Patent(Industrial Property Rights)] PLATINUM COMPLEX COMPOUND AND UTILIZATION OF THE SAME (2010)
  • Inventor(s): 米田誠治, 千熊正彦
  • Industrial Property Rights Holder: 天真堂製薬(株), (株)ヤクルト本社
  • Filing Date: 2010-07-24
  • Overseas
• [Patent(Industrial Property Rights)] PLATINUM COMPLEX COMPOUND AND UTILIZATION OF THE SAME (2010)
  • Inventor(s): 米田誠治, 千熊正彦
  • Industrial Property Rights Holder: 天真堂製薬(株), (株)ヤクルト本社
  • Filing Date: 2010-08-05
  • Overseas
• [Patent(Industrial Property Rights)] PLATINUM COMPLEX COMPOUND AND UTILIZATION OF THE SAME (2010)
  • Inventor(s): 米田誠治, 千熊正彦
  • Industrial Property Rights Holder: 天真堂製薬(株), (株)ヤクルト本社
  • Filing Date: 2010-08-11
  • Overseas
• [Patent(Industrial Property Rights)] PLATINUM COMPLEX COMPOUND AND UTILIZATION OF THE SAME (2010)
  • Inventor(s): 米田誠治, 千熊正彦
  • Industrial Property Rights Holder: 天真堂製薬(株), (株)ヤクルト本社
  • Filing Date: 2010-07-14
  • Overseas