Development of triple-target antitumor drugs recognized by oligopeptide transporters

• Project/Area Number: 23659019
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Physical pharmacy
• Research Institution: Kanazawa University
• Principal Investigator: KATO Yukio 金沢大学, 薬学系, 教授 (30251440)
• Co-Investigator(Renkei-kenkyūsha): NAKAMICHI Noritaka 金沢大学, 薬学系, 准教授 (10401895) ; SUGIURA Tomoko 金沢大学, 薬学系, 助教 (70542190) ; WAKAYAMA Tomohiko 金沢大学, 医学系, 准教授 (70305100)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ペプチド / トランスポーター / PDZアダプター / 抗腫瘍薬 / 生体膜透過

Research Abstract

Transporters play pivotal roles in both uptake of nutrients and efflux of metabolites/xenobiotics in the body. Oligopeptide transporters (PEPT) function as an uptake mechanism for both dipeptides and tripeptides. PEPTs are known to be highly expressed in a certain types of cancer cells probably to maintain its extremely rapid growth by uptake of nutrients. We have previously succeeded in synthesis of both tumor-imaging substrate and anti-tumor peptides targeted to PEPTs. In the present study we aimed to establish antitumor drugs with triple targets of PEPTs and its associated proteins.

Research Products

• [Journal Article] メタボロミクスによるトランスポーター機能の探索 (2012)
  • Author(s): 杉浦智子、加藤将夫
  • Journal Title: 細胞工学 Volume: 31 Pages: 546-547
  • URL: http://gakken-mesh.jp/journal/detail/9784780901306.html
• [Journal Article] PDZ adaptors : their regulation of epithelial transporters and involvement in human disease (2011)
  • Author(s): Sugiura T, Shimizu T, Kijima A, Minakata S, Kato Y
  • Journal Title: J Pharm Sci Volume: 100(9) Issue: 9 Pages: 3620-3635
  • DOI: 10.1002/jps.22575
  • NAID: 120003308592
  • Peer Reviewed
• [Journal Article] DZK1 regulates breast cancer resistance protein in small intestine (2011)
  • Author(s): Shimizu, T., Sugiura, T., Wakayama, T.,Kijima, A., Nakamichi, N., Iseki, S.,Silver, D.L., Kato, Y
  • Journal Title: Drug Metab. Dispos Volume: 39 Issue: 11 Pages: 2148-2154
  • DOI: 10.1124/dmd.111.040295
  • Peer Reviewed
• [Journal Article] Pharmacokinetics and hepatic uptake of eltrombopag, a novel platelet-increasing agent (2011)
  • Author(s): Takeuchi, K., Sugiura, T., Umeda, S.,Matsubara, K., Horikawa, M., Nakamichi, N., Silver, D.L., Ishiwata, N., Kato, Y
  • Journal Title: Drug Metab. Dispos Volume: 39 Issue: 6 Pages: 1088-1096
  • DOI: 10.1124/dmd.110.037960
  • Peer Reviewed
• [Presentation] 選択的物質吸収と生体防御に働くトランスポーター複合体 (2012)
  • Author(s): 加藤将夫
  • Organizer: 東京大学大学院薬学系研究科分子薬物動態学教室 第40回ミニシンポジウム/創剤フォーラム特別講演会「薬物動態学・医薬品評価科学の現状と今後の展望」(招待講演)
  • Place of Presentation: 東京大学武田先端知ビル(東京都)
  • Year and Date: 2012-03-16
• [Presentation] Interaction of breast cancer resistance protein (BCRP/ABCG2) with PDZ adaptor PDZK1 and therapeutic agents in small intestine (2012)
  • Author(s): Takuya Shimizu, Tomoko Sugiura, Tomohiko Wakayama, Noritaka Nakamichi, Shoichi Iseki, David L. Silver and Yukio Kato
  • Organizer: Globalization of Pharmaceutics Education Network (GPEN) Meeting 2012
  • Place of Presentation: Monash University (Melbourne, Australia)
• [Presentation] トランスポーターと医薬品毒性の複雑な関係 (2012)
  • Author(s): 加藤将夫
  • Organizer: 安全性評価研究会2012八ヶ岳フォーラム
  • Place of Presentation: 八ヶ岳自然文化園セミナーハウス (長野県)(招待講演)
• [Presentation] トランスポーターと医薬品毒性の複雑な関係 (2012)
  • Author(s): 加藤将夫
  • Organizer: 安全性評価研究会2012八ヶ岳フォーラム
  • Place of Presentation: 八ヶ岳自然文化園セミナーハウス (長野県)
  • Invited
• [Presentation] PDZ adaptor PDZK1 is a functional regulator of breast cancer resistance protein (BCRP/ABCG2) in small intestine. (2012)
  • Author(s): Takuya Shimizu, Tomoko Sugiura, Tomohiko Wakayama, Noritaka Nakamichi, Shoichi Iseki, David L. Silver, and Yukio Kato.
  • Organizer: International Symposium on Epithelial Barrier and Transport 2012
  • Place of Presentation: Ritsumeikan University (滋賀県)
• [Presentation] Interaction of breast cancer resistance protein (BCRP/ABCG2) with PDZ adaptor PDZK1 and therapeutic agents in small intestine. (2012)
  • Author(s): Takuya Shimizu, Tomoko Sugiura, Tomohiko Wakayama, Noritaka Nakamichi, Shoichi Iseki, David L. Silver, and Yukio Kato.
  • Organizer: Globalization of Pharmaceutics Education Network (GPEN) Meeting 2012
  • Place of Presentation: Monash University (Melbourne, Australia)
• [Presentation] 選択的物質吸収と生体防御に働くトランスポーター複合体 (2012)
  • Author(s): 加藤将夫
  • Organizer: 東京大学大学院薬学系研究科分子薬物動態学教室 第40回ミニシンポジウム／創剤フォーラム特別講演会「薬物動態学・医薬品評価科学の現状と今後の展望」(招待講演)
  • Place of Presentation: 東京大学武田先端知ビル （東京都）
• [Presentation] トランスポーターの関わる消化器毒性とその機序 (2011)
  • Author(s): 加藤将夫
  • Organizer: 第38回日本トキシコロジー学会学術年会ワークショップ3「トランスポーターの関わる薬剤誘起性の副作用機構の解明と医薬品開発過程における予測法の確立」(招待講演)
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-07-13
• [Presentation] トランスポーターの関わる消化器毒性とその機序 (2011)
  • Author(s): 加藤将夫
  • Organizer: 第38回日本トキシコロジー学会学術年会 ワークショップ3「トランスポーターの関わる薬剤誘起性の副作用機構の解明と医薬品開発過程における予測法の確立」(招待講演)
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Book] Chapter 10 PEPT (SLC15A) family (2013)
  • Author(s): Sugiura T, Umeda S, Tsuji A, Kato Y
• [Book] Pharmacogenomics of Human Drug Transporters (2013)
  • Author(s): Sugiura T, Umeda S, Tsuji A, Kato Y.
  • Total Pages: 20
  • Publisher: PEPT (SLC15A) family
• [Remarks]
  • URL: http://www.p.kanazawa-u.ac.jp/~bunyaku/
• [Remarks]
  • URL: http://www.p.kanazawa-u.ac.jp/~bunyaku/