QT Interval Prolongation: And the Beat Goes on

Mehran      Jalaie; Daniel   D.   Holsworth

doi:10.2174/138955705774933338

Abstract

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 IKr 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.

Keywords: HERG, QT, Torsade de Pointes, Ion Channels, Homology, Docking, QSAR, High Throughput Screen