title: QT interval prolongation: and the beat goes on.
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 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.
authors.affiliation: Pfizer Global Research & Development, Michigan Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. mehran.jalaie@pfizer.com
authors.forename: Mehran
authors.initials: M
authors.lastname: Jalaie
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Holsworth
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004594:Electrophysiology; D006321:Heart / Q000502:physiology; D006801:Humans; D008133:Long QT Syndrome / Q000503:physiopathology*; D008955:Models, Cardiovascular; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects* / Q000502:physiology; D021281:Quantitative Structure-Activity Relationship; D018570:Risk Assessment; D016171:Torsades de Pointes / Q000503:physiopathology*
chemical_list: D000889:Anti-Arrhythmia Agents; D024642:Potassium Channels, Voltage-Gated