Animal models of xenobiotic receptors in drug metabolism and diseases

被引:26
作者
Gong, HB [1 ]
Sinz, MW
Feng, Y
Chen, TS
Venkataramanan, R
Xie, W
机构
[1] Univ Pittsburgh, Ctr Pharmacogenet, Sch Pharm, Pittsburgh, PA 15260 USA
[2] Bristol Myers Squibb Co, Metab & Pharmacokinet, Wallingford, CT 06492 USA
[3] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA USA
[4] Bristol Myers Squibb Co, Lead Discovery & Profiling, Wallingford, CT 06492 USA
来源
PHASE II CONJUGATION ENZYMES AND TRANSPORT SYSTEMS | 2005年 / 400卷
基金
美国国家卫生研究院;
关键词
D O I
10.1016/S0076-6879(05)00034-0
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Drug-metabolizing enzymes, including phase 11 conjugating enzymes, play an important role in both drug metabolism and human diseases. The genes that encode these enzymes and transporters are inducible by numerous xenobiotics and endobiotics and the inducibility shows clear species specificity. In the past several years, orphan nuclear receptors, such as PXR and CAR, have been established as species-specific "xenobiotic receptors" that regulate the expression of phase I and phase 11 enzymes and drug transporters. The creation of xenobiotic receptor transgenic and knockout mice has not only provided an opportunity to dissect the transcriptional control of drug metabolizing enzymes, but also offered a unique opportunity to study the xenobiotic receptor-mediated enzyme regulation in both drug metabolism and diseases. "Humanized" hPXR transgenic mice represent a major step forward in the creation and utilization of humanized rodent models for toxicological assessment that may aid in the development of safer drugs.
引用
收藏
页码:598 / +
页数:22
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