中国科学院大连化学物理研究所机构知识库
Advanced  
DICP OpenIR  > 中国科学院大连化学物理研究所  > 期刊论文
题名: A Naturally Occurring Isoform-Specific Probe for Highly Selective and Sensitive Detection of Human Cytochrome P450 3A5
作者: Wu, Jing-Jing1;  Cao, Yun-Feng1, 2;  Feng, Liang1;  He, Yu-Qi3;  Hong, James Y.4;  Dou, Tong-Yi1;  Wang, Ping1;  Hao, Da-Cheng5;  Ge, Guang-Bo1;  Yang, Ling6
刊名: JOURNAL OF MEDICINAL CHEMISTRY
发表日期: 2017-05-11
DOI: 10.1021/acs.jmedchem.7b00001
卷: 60, 页:3804-3813
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Life Sciences & Biomedicine
类目[WOS]: Chemistry, Medicinal
研究领域[WOS]: Pharmacology & Pharmacy
英文摘要: Cytochrome P450 (CYP) 3A5 characterized with polymorphic and extensive expression in multiple tissues is the most important P450 enzyme among the minor CYP3A isoforms. However, a selective and sensitive probe for CYP3A5 remains unavailable. In this study, we identified and characterized a naturally occurring lignan 12 (schisantherin E) as an isoform-specific probe for selective detection of CYP3A5 activity in complex biological samples. With thorough characterization including LC-MS and NMR, we found that 12 can be metabolized by CYP3A5 to generate a major metabolite 2-O-demethylated 12. Meanwhile, both reaction phenotyping and chemical inhibition experiments further revealed that CYP3A5 selectively catalyzed the 2-O-demethylation of 12. Specifically, the interactions between the Phe210 residue of CYP3A5 and methyl benzoate of 12 might play key roles in 12-O-demethylation, which was revealed by docking simulation and site-directed mutagenesis studies. These findings are beneficial for exploring the role of CYP3A5 in drug metabolism and pathologic process.
关键词[WOS]: HUMAN LIVER-MICROSOMES ;  IN-VITRO METABOLISM ;  CYP3A5 ;  P450 ;  EXPRESSION ;  IDENTIFICATION ;  INACTIVATION ;  INHIBITION ;  ENZYMES ;  MARKERS
语种: 英语
WOS记录号: WOS:000401403100019
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/152282
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Peoples R China
2.Key Lab Liaoning Tumor Clin Metabol, Jinzhou, Liaoning, Peoples R China
3.Zunyi Med Univ, Minist Educ, Key Lab Basic Pharmacol, Sch Pharm, Zunyi 563000, Guizhou, Peoples R China
4.Univ Illinois, Dept Biopharmaceut Sci, Chicago, IL 60612 USA
5.Dalian Jiaotong Univ, Sch Environm & Chem Engn, Dalian 116028, Peoples R China
6.Shanghai Univ Tradit Chinese Med, Shanghai 201203, Peoples R China

Recommended Citation:
Wu, Jing-Jing,Cao, Yun-Feng,Feng, Liang,et al. A Naturally Occurring Isoform-Specific Probe for Highly Selective and Sensitive Detection of Human Cytochrome P450 3A5[J]. JOURNAL OF MEDICINAL CHEMISTRY,2017,60:3804-3813.
Service
 Recommend this item
 Sava as my favorate item
 Show this item's statistics
 Export Endnote File
Google Scholar
 Similar articles in Google Scholar
 [Wu, Jing-Jing]'s Articles
 [Cao, Yun-Feng]'s Articles
 [Feng, Liang]'s Articles
CSDL cross search
 Similar articles in CSDL Cross Search
 [Wu, Jing-Jing]‘s Articles
 [Cao, Yun-Feng]‘s Articles
 [Feng, Liang]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
  Add to CiteULike  Add to Connotea  Add to Del.icio.us  Add to Digg  Add to Reddit 
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Powered by CSpace