Cytochrome P450 4A Isoform Inhibitory Profilie of N-Hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine (HET0016), a Selective Inhibitor of 20-HETE Synthesis
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- Seki Takayuki
- Medicinal Pharmacology Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd.
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- Wang Mong-Heng
- Department of Physiology, Medical College of Georgia
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- Miyata Noriyuki
- Medicinal Pharmacology Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd.
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- Laniado-Schwartzman Michal
- Department of Pharmacology, New York Medical College
書誌事項
- タイトル別名
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- Cytochrome P450 4A Isoform Inhibitory Profile of N-Hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine (HET0016), a Selective Inhibitor of 20-HETE Synthesis
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抄録
We examined the effect of N-hydroxy-N′-(4-butyl-2-methylphenyl)-formamidine) (HET0016), an inhibitor of 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) synthesis on the ω-hydroxylation and epoxidation of arachidonic acid (AA) catalyzed by recombinant cytochrome P450 4A1 (CYP4A1), CYP4A2 and CYP4A3, and characterized the enzyme inhibitory profile of HET0016. The IC50 values of HET0016 for recombinant CYP4A1-, CYP4A2- and CYP4A3-catalyzed 20-HETE synthesis averaged 17.7 nM, 12.1 nM and 20.6 nM, respectively. The IC50 value for production of 11,12-epoxy-5,8,14-eicosatrienoic acid (11,12-EET) by CYP4A2 and 4A3 averaged 12.7 nM and 22.0 nM, respectively. The IC50 value for CYP2C11 activity was 611 nM which was much greater than that for CYP4As. The initial velocity study showed the Ki value of HET0016 for CYP4A1 was 19.5 nM and a plot of Vmax versus amount of recombinant CYP4A1 added shows HET0016 is an irreversible non-competitive inhibitor. These results indicate that HET0016 is a selective, non-competitive and irreversible inhibitor of CYP4A.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 28 (9), 1651-1654, 2005
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204625767936
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- NII論文ID
- 110003666485
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 7409593
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- PubMed
- 16141533
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
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