Drugs, hERG and sudden death.
نویسنده
چکیده
Early recognition of potential QT/TdP liability is now an essential component of the drug discovery/drug development program. The hERG assay is an indispensable step and a high-quality assay must accompany any investigational new drug (IND) application. While it is the gold standard at present, the hERG assay is too labor-intensive and too low throughput to be used as a screen early in the discovery/development process. A variety of indirect high throughput screens have been used.
منابع مشابه
Anti-HERG activity and the risk of drug-induced arrhythmias and sudden death.
AIMS Drug-induced QTc-prolongation, resulting from inhibition of HERG potassium channels may lead to serious ventricular arrhythmias and sudden death. We studied the quantitative anti-HERG activity of pro-arrhythmic drugs as a risk factor for this outcome in day-to-day practice. METHODS AND RESULTS All 284,426 case reports of suspected adverse drug reactions of drugs with known anti-HERG acti...
متن کاملDrug trapping in hERG K+ channels: (not) a matter of drug size?† †The authors declare no competing interests.
Inhibition of hERG K channels by structurally diverse drugs prolongs the ventricular action potential and increases the risk of torsade de pointes arrhythmias and sudden cardiac death. The capture of drugs behind closed channel gates, so-called drug trapping, is suggested to harbor an increased pro-arrhythmic risk. In this study, the trapping mechanisms of a trapped hERG blocker propafenone and...
متن کاملDrug trapping in hERG K+ channels: (not) a matter of drug size?
Inhibition of hERG K+ channels by structurally diverse drugs prolongs the ventricular action potential and increases the risk of torsade de pointes arrhythmias and sudden cardiac death. The capture of drugs behind closed channel gates, so-called drug trapping, is suggested to harbor an increased pro-arrhythmic risk. In this study, the trapping mechanisms of a trapped hERG blocker propafenone an...
متن کاملDissociative States: hERG Channel (Kv11.1) Modulators That Enhance Dissociation of Drugs From Their Blocking Receptor: Potential New Therapeutic Drugs.
Sudden cardiac death secondary to drug-induced long QT syndrome is a major safety concern and has led to withdrawal of several high-profile drugs, such as cisapride and astemizole, from the market. Although these drugs have different chemical structures, they all block the rapid delayed rectifier K current (I Kr ) with high potency. The hERG channel (Kv11.1) encoded by the hERG gene is responsi...
متن کاملDissociative States: hERG Channel (Kv11.1) Modulators That Enhance Dissociation of Drugs From Their Blocking Receptor
Sudden cardiac death secondary to drug-induced long QT syndrome is a major safety concern and has led to withdrawal of several high-profile drugs, such as cisapride and astemizole, from the market. Although these drugs have different chemical structures, they all block the rapid delayed rectifier K current (I Kr ) with high potency. The hERG channel (Kv11.1) encoded by the hERG gene is responsi...
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ورودعنوان ژورنال:
- Cell calcium
دوره 35 6 شماره
صفحات -
تاریخ انتشار 2004