CYP on a Chip ~Rapid Evaluation of CYP Drug Metabolism with Silver Chip Electrode~

• Project/Area Number: 23659023
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Physical pharmacy
• Research Institution: Osaka University
• Principal Investigator: UNO Tadayuki 大阪大学, 大学院・薬学研究科, 教授 (00183020)
• Research Collaborator: 宮本 正芳 大阪大学, 大学院・薬学研究科, 博士前期課程 ; 野出 純一 大阪大学, 大学院・薬学研究科, 博士前期課程 ; 小泉 温史 大阪大学, 大学院・薬学研究科, 博士前期課程 ; 山田 麻由 大阪大学, 薬学部, 薬学科 ; 小宮山 祐美 大阪大学, 薬学部, 薬学科
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: シトクロムP450 / 薬物代謝 / 一塩基多型 / 電気化学 / 酸化還元電位 / 薬剤反応性

Research Abstract

Cytochrome P450 (CYP) is a group of enzymes that play key roles in the drug metabolism in human, but comprehensive studies of CYP have been very difficult, because CYP enzymes contain various isoforms and their drug specificities are quite low. In this study, I aimed at construction of evaluating system for CYP drug metabolism electrochemically. Charging an electric potential for CYP reduction, silver electrode was found to produce silver oxide, and hence I used gold electrode which is more stable than silver. Applying various coating reagents, I found that a mixed solution containing mercaptoundecanoic acid and mercaptoundecanol could result in measurement of redox wave of CYP2C9.

Research Products

• [Journal Article] Comparison of Cytochrome P450 Mediated Metabolism of Three CNS Acting Drugs (2012)
  • Author(s): Tamer Zekry Attia, Taku Yamashita, Masayoshi Miyamoto, Atsushi Koizumi, Yuki Yasuhara, Jun-ichi Node, Yumi Erikawa, Yumi Komiyama, Chiaki Horii, Mayu Yamada, Mahmoud Ahmad Omar, OsamaHassan Abdelmageed, Sayed Mohamed Derayea, and Tadayuki Uno
  • Journal Title: Chem. Pharm. Bull Volume: 60 Pages: 1544-1549
  • URL: https://www.jstage.jst.go.jp/article/cpb/60/12/60_c12-00719/_article
• [Presentation] Construction of novel sensitive system to evaluate drug affinities for CYPs with Ag/Au nanoparticles (2013)
  • Author(s): Takashi NAKAMURA, Yumi KOMIYAMA, Hirofumi TSUJINO, Taku YAMASHITA, and Tadayuki UNO
  • Organizer: 第23回金属の関与する生体関連反応シンポジウム
  • Place of Presentation: 西東京
  • Year and Date: 2013-06-21
• [Presentation] Comparison of Cytochrome P450 Mediated Metabolism of Three CNS Acting Drugs (2012)
  • Author(s): Taku Yamashita, Tamer Zekry Attia, Masayoshi Miyamoto, Atsushi Koizumi, Yuki Yasuhara, Jun-ichi Node, Yumi Erikawa, Yumi Komiyama, Chiaki Horii, Mayu Yamada, Mahmoud Ahmad Omar, Osama Hassan Abdelmageed, Sayed Mohamed Derayea, and Tadayuki Uno
  • Organizer: 50th Anniversary Symposium on Cytochrome P450 in Fukuoka
  • Place of Presentation: Fukuoka
  • Year and Date: 2012-12-03
• [Presentation] Construction of Ag nanoparticle system sensitive to the active site structure in heme oroteins (2011)
  • Author(s): 宇野公之、小宮山祐美、金森美果、山下沢、青山浩
  • Organizer: 第21回金属の関与する生体関連反応シンポジウム
  • Place of Presentation: 千葉
  • Year and Date: 2011-05-30
• [Remarks]
  • URL: http://www.phs.osaka-u.ac.jp/homepage/b006/