Chain Reaction of Drug Metabolism -A Comprehensive Study on the Cooperative and Competitive Drug Metabolism by CYP Isoforms
| Project/Area Number |
23390011
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | Osaka University |
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Principal Investigator |
UNO Tadayuki 大阪大学, 薬学研究科(研究院), 教授 (00183020)
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| Co-Investigator(Kenkyū-buntansha) |
AOYAMA Hiroshi 大阪大学, 大学院・薬学研究科, 准教授 (60291910)
YAMASHITA Taku 大阪大学, 大学院・薬学研究科, 招聘准教授 (70398246)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2013: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2012: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2011: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Keywords | 薬物代謝 / シトクロムＰ４５０ / 一塩基多型 / 共鳴ラマン分光 / シトクロムP450 / X線結晶構造解析 |
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| Research Abstract |
Cytochrome P450s (CYPs) play a key role in human drug metabolism, and five CYP isoforms can metabolize more than 90% of clinical drugs in the market. In this study, we focused on a chain reaction of drug metabolism played by five isoforms. Although an anti-depressant amitriptyline is mainly metabolized by CYP1A2, 2C19, and 2D6, its metabolite nortriptyline, which is structurally similar to amitriptyline, was found to be poorly metabolized by these isoforms. On the other hand, CYP2C9 is a poor metabolizer of amitriptyline although it is homologous with 2C19 in amino acid sequence and three dimensional structure. We revealed that the drug specificity is regulated by the basicity of an amino acid residue at position 72.
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Effect of Cytochrome P450 2C19 and 2C9 Amino Acid Residues 72 and 241 on Metabolism of Tricyclic Antidepressant Drugs2014
Author(s)
Tamer Zekry Attia, Taku Yamashita, Mohamed Abdelkhalek Hammad, Akinori Hayasaki, Takumi Sato, Masayoshi Miyamoto, Yuki Yasuhara, Takashi Nakamura, Yusuke Kagawa, Hirofumi Tsujino, Mahmoud Ahmed Omar, Osama Hassan Abdelmageed, Sayed Mohamed Derayea, Tadayuki Uno
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Journal Title
CHEMICAL & PHARMACEUTICAL BULLETIN
Volume: 62巻
Issue: 2
Pages: 176-181
DOI
NAID
ISSN
0009-2363, 1347-5223
Related Report
Peer Reviewed
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[Journal Article] Comparison of Cytochrome P450 Mediated Metabolism of Three Central Nervous System Acting Drugs2012
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, Osama Hassan Abdelmageed, Sayed Mohamed Derayea, Tadayuki Uno
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Journal Title
CHEMICAL & PHARMACEUTICAL BULLETIN
Volume: 60巻
Issue: 12
Pages: 1544-1549
DOI
NAID
ISSN
0009-2363, 1347-5223
Related Report
Peer Reviewed
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