Raschi Emanuel, Vasina Valentina, Poluzzi Elisabetta, De Ponti Fabrizio
Department of Pharmacology, University of Bologna, Via Irnerio, 48, I-40126 Bologna BO, Bologna, Italy.
Pharmacol Res. 2008 Mar;57(3):181-95. doi: 10.1016/j.phrs.2008.01.009. Epub 2008 Feb 2.
The human ether-à-go-go related gene (hERG) K+ channel is of great interest for both basic researchers and clinicians because its blockade by drugs can lead to QT prolongation, which is a risk factor for torsades de pointes, a potentially life-threatening arrhythmia. A growing list of agents with "QT liability" have been withdrawn from the market or restricted in their use, whereas others did not even receive regulatory approval for this reason. Thus, hERG K+ channels have become a primary antitarget (i.e. an unwanted target) in drug development because their blockade causes potentially serious side effects. On the other hand, the recent identification and functional characterization of hERG K+ channels not only in the heart, but also in several other tissues (e.g. neurons, smooth muscle and cancer cells) may have far reaching implications for drug development for a possible exploitation of hERG as a target, especially in oncology and cardiology.
人醚 - 去极化相关基因（hERG）钾通道对基础研究人员和临床医生都具有极大的吸引力，因为药物对其的阻断可导致QT间期延长，这是尖端扭转型室速的一个危险因素，而尖端扭转型室速是一种潜在的危及生命的心律失常。越来越多具有“QT风险”的药物已被撤出市场或其使用受到限制，还有一些药物甚至因此未获得监管批准。因此，hERG钾通道已成为药物研发中的主要非靶标（即不受欢迎的靶点），因为对其的阻断会导致潜在的严重副作用。另一方面，最近对hERG钾通道不仅在心脏，而且在其他几种组织（如神经元、平滑肌和癌细胞）中的鉴定和功能表征，可能对药物研发具有深远影响，因为有可能将hERG作为一个靶点加以利用，特别是在肿瘤学和心脏病学领域。
