Human characteristic mechanism of enzyme induction and the prediction

人体特有的酶诱导机制及预测

• 批准号: 13470510
• 负责人: YAMAZOE Yasushi
• 金额: $ 9.15万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470510/
• 关键词: enzyme induction; stable expression; CYP3A4; human drug metabolism; PXR; 誘導評価系; 安定発現株; レポーターアッセイ; スクリーニング; in vivo; CYP3A; cyt.P450; Induction; PXR

As an estimation tool for human CYP3A4 induction, we have succeeded to make an adenovirus vecter system including CYP3A4 promoter and enhancer regions. The vecter was used to obtain the stably active clones in HepG2 cells. Among the clones selected, couple clones responded to typical chemical induces and showed high luciferase reporter activities. These clones are found to be candidates as effective tools for the quantitative prediction of inducing potential for human CYP3A4. We are currently evaluating the clones for the practical tools.

我们成功构建了包含CYP3A4启动子和增强子区域的腺病毒载体系统，作为人CYP3A4诱导的估计工具。利用该载体在HepG2细胞中获得稳定的活性克隆。在所选无性系中，偶对典型化学诱导有应答，荧光素酶报告活性较高。这些克隆被认为是定量预测人类CYP3A4诱导潜能的有效工具。我们目前正在为实用工具评估克隆。

项目成果

M.Furukawa: "Adenovirus vector-mediated reporter system for in vivo analysis of the human CYP3A4 gene activation"J. Biochem.. 131. 71-78 (2002)

M.Furukawa：“腺病毒载体介导的报告系统用于体内分析人CYP3A4基因激活”J。

M.Shimada: "A hydroxysteroid sulfotransferase, St2b2, in a skin cholesterol sulfotransferase in mice"J. Biochem.. 131. 167-169 (2002)

M.Shimada：“小鼠皮肤胆固醇磺基转移酶中的羟基类固醇磺基转移酶 St2b2”J.

S.Matsumoto: "Involvement of CYP2J2 on the intestinal first-pass metabolism of antihistamine drug, astemizole"Drug Metab. Dispos.. 30. 1240-1245 (2002)

S.Matsumoto：“CYP2J2 参与抗组胺药物阿司咪唑的肠道首过代谢”Drug Metab。

M.Ogino: "Selective suppression of human CYP3A form, CYP3A7, by troglitazone in HepG2 cells"Drug Metab. Pharmacokin.. 17. 42-46 (2002)

M.Ogino：“曲格列酮在 HepG2 细胞中选择性抑制人 CYP3A 形式 CYP3A7”Drug Metab。

M.Ogino: "Selective suppressions of human CYP3A forms, CYP3A5 and CYP3A7, by troglitazone in HepG2 cells"Drug Metabol. Pharmacokin.. 17. 42-46 (2002)

M.Ogino：“曲格列酮在 HepG2 细胞中选择性抑制人 CYP3A 形式、CYP3A5 和 CYP3A7”药物代谢。