| Project/Area Number |
03557113
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Keio University |
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Principal Investigator |
KATO Ryuichi Keio Univ., Sch. of Med., Professor, 医学部, 教授 (40112685)
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| Co-Investigator(Kenkyū-buntansha) |
MIYADO Shinji Meiji Seika Kaisha, LTD,Pharmaceutical Research Center, Group Leader, 薬品総合研究所探索研究所, 室長
MURAYAMA Norie Keio Univ., Sch. of Med., Assistant, 医学部, 助手 (90219949)
NAGATA Miki Keio Univ., Sch. of Med., Assistant, 医学部, 助手 (10196488)
NAGATA Kiyoshi Keio Univ., Sch. of Med., Assistant, 医学部, 助手 (80189133)
YAZUMORI Toshio Keio Univ., Sch. of Med., Assistant, 医学部, 助手 (70182350)
甲斐 文夫 明治製菓(株)薬品総合研究所新薬研究所, 所長
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥15,200,000 (Direct Cost: ¥15,200,000)
Fiscal Year 1992: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 1991: ¥9,900,000 (Direct Cost: ¥9,900,000)
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| Keywords | Cytochrome P-450 / Gene expression / Human drug metabolism / P-450 mixture / 薬物代謝 / 薬物代謝酵素 / 異所的発現 / ヒト薬物代謝能 / チトクロムP-450 |
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| Research Abstract |
The purpose of this project is development of a new assessment method for human drug metabolism by using mixture of cytochrome P-450 expressed in yeast cells. We first cloned CYP3A4, a major human cytochrome P-450, and expressed it in yeast cells. On the other hand, we expressed human NADPH-cytochrome P-450 reductase and cytochrome b_5 in yeast cells. Then we improved the expression vectors to co-express different vectors in the same cells . We succeeded in co-expressing CYP3A4, NADPH-cytochrome P-450 reductase and cytochrome b_5 in the same cells and we observed high enzymic activities for several substrates. These results indicates further possible way to express sever al different cytochrome P-450 by this method.
We, then, try to increase the yield of cytochrome P-450 in yeast cells changing by conditions of the incubation. Thus, we concluded that this approach is useful method for the assessment of human drug metabolism by using a mixture of human cytochrome P-450 expressed in yeast cells.
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