QT interval prolongation: And the beat goes on

被引:15
作者
Jalaie, M [1 ]
Holsworth, DD [1 ]
机构
[1] Pfizer Global Res & Dev, Michigan Labs, Ann Arbor, MI 48105 USA
关键词
HERG; QT; torsade de pointes; ion channels; homology; docking; QSAR; high throughput screen;
D O I
10.2174/138955705774933338
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Consideration of QT interval prolongation and the risk for developing torsade de pointes is a critical issue in the evaluation of new bioactive agents. Over the past several years, there has been a dramatic increase in understanding the I-Kr channel and its role in the duration of the action potential and cardiac repolarization. Furthermore, a variety of factors and situations have been identified that can increase the risk of QT interval prolongation. In this brief summary, an overview of the hERG channel and QT prolongation will be presented. The basic electro-physiology of the heart, the related action potentials, and pre-clinical assays is reviewed. Further, an introduction to the current status of in silico efforts in predicting potential hERG blockers is discussed. Lastly, the strengths and weaknesses of each modeling method is presented along with insight to the appropriate use of each model.
引用
收藏
页码:1083 / 1091
页数:9
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