Allosteric Modulation of K(v)11.1 (hERG) Channels Protects Against Drug-Induced Ventricular Arrhythmias

Yu Zhiyi; Liu Jia; van Veldhoven Jacobus P. D.; IJzerman Adriaan P.; Schalij Martin J.; Pijnappels Daniel A.; Heitman Laura H.; de Vries Antoine A. F.

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Allosteric Modulation of K(v)11.1 (hERG) Channels Protects Against Drug-Induced Ventricular Arrhythmias

机译：K（v）11.1（hERG）通道的变构调节可防止药物引起的室性心律失常

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Background Ventricular arrhythmias as a result of unintentional blockade of the K(v)11.1 (hERG [human ether-a-go-go-related gene]) channel are a major safety concern in drug development. In past years, several highly prescribed drugs have been withdrawn for their ability to cause such proarrhythmia. Here, we investigated whether the proarrhythmic risk of existing drugs could be reduced by K(v)11.1 allosteric modulators.

机译：背景技术由于无意识地阻滞了K（v）11.1（hERG（人类醚-go-go-相关基因）通道）而导致的室性心律失常是药物开发中的主要安全问题。在过去的几年中，已经取消了几种处方药，因为它们具有引起这种心律失常的能力。在这里，我们调查了现有药物的心律失常风险是否可以通过K（v）11.1变构调节剂降低。

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《Circulation. Arrhythmia and electrophysiology》 |2016年第4期|共11页
作者
Yu Zhiyi; Liu Jia; van Veldhoven Jacobus P. D.; IJzerman Adriaan P.; Schalij Martin J.; Pijnappels Daniel A.; Heitman Laura H.; de Vries Antoine A. F.;
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正文语种 eng
中图分类产科学;
关键词
arrhythmias; cardiac; cardiotoxicity; cell culture techniques; myocytes; cardiac; potassium voltage-gated channel; subfamily H; member 2; radioligand assay; voltage-sensitive dye imaging;

机译：心律失常;心脏;心脏毒性;细胞培养技术;心肌细胞;心脏;钾电压门控通道;H亚家族;成员2;放射配体测定;压敏染料成像;

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1. Allosteric Modulation of K(v)11.1 (hERG) Channels Protects Against Drug-Induced Ventricular Arrhythmias [J] . Yu Zhiyi, Liu Jia, van Veldhoven Jacobus P. D., Circulation. Arrhythmia and electrophysiology . 2016,第4期

机译：K（v）11.1（hERG）通道的变构调节可防止药物引起的室性心律失常
2. hERG (KCNH2 or Kv11.1) K+ Channels: Screening for Cardiac Arrhythmia Risk [J] . Mark R. Bowlby Ravi Peri Howard Zhang John Dunlop Current Drug Metabolism . 2008,第9期

机译：hERG（KCNH2或Kv11.1）K +通道：筛查心脏心律失常风险
3. Synthesis and biological evaluation of negative allosteric modulators of the K(v)11.1(hERG) channel [J] . Yu Zhiyi, van Veldhoven Jacobus P. D., t Hart Ingrid M. E., European Journal of Medicinal Chemistry: Chimie Therapeutique . 2015,第Null期

机译：K（v）11.1（hERG）通道的负变构调节剂的合成和生物学评估
4. Drug-induced QT interval prolongation - regulatory guidance and perspectives on hERG channel studies [C] . Rashmi R Shah symposium on The hERG cardiac potassium channel: structure, function, and long QT syndrome . 2005

机译：药物诱导的QT间隔延长 - 监管指导和HERG渠道研究的观点
5. Computational Modeling of Sex-Based Differences in Drug-Induced Cardiac Ventricular Arrhythmias [D] . Hartman-Kenzler, Jacob 2018

机译：药物诱发的心脏室性心律失常中基于性别的差异的计算模型
6. Modulation of Kv11.1 (hERG) channels by 5‐(((1H–indazol‐5‐yl)oxy)methyl)‐N‐(4‐(trifluoromethoxy)phenyl)pyrimidin‐2‐amine (ITP‐2) a novel small molecule activator [O] . Harinath Sale, Samrat Roy, Jayakumar Warrier, 2017

机译：5-（（（（1H-indazol-5-yl）oxy）methyl）N-（4-（trifluoromethoxymethoxy）phenyl）pyrimidin-2-amine（ITP-2）对Kv11.1（hERG）通道的调节新型小分子活化剂
7. Allosteric Modulation of K v 11.1 (hERG) Channels Protects Against Drug-Induced Ventricular Arrhythmias [O] . Zhiyi Yu, Jia Liu, Jacobus P.D. van Veldhoven, 2016

机译：K V 11.1（HERG）通道的变构调制保护药物诱导的心间心律失常

Allosteric Modulation of K(v)11.1 (hERG) Channels Protects Against Drug-Induced Ventricular Arrhythmias

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