General Pharmacology Group, Department of Drug Discovery Support, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
Br J Pharmacol. 2010 Jan;159(1):22-4. doi: 10.1111/j.1476-5381.2009.00265.x.
In drug development, early recognition of a potential for blocking the human ether-a-go-go related gene (hERG) channels is perhaps the best way to avoid later disappointment when QT interval prolongation shows up in clinical trials. Knowledge of the hERG blocking liability offers the chance to modify the molecule to reduce, or even eliminate, this unwanted activity and lack of success in such modification is a good reason to stop further development of the molecule. In this issue of the , different methods for early detection of hERG channel blocking liability are discussed by Pollard One attractive approach is widespread screening of molecules at a very early stage of research to detect compounds with this liability and thereby eliminate them. There are now several methodologies available that offer hERG channel testing on a high-throughput format but entail a diverse selection of direct and indirect readouts of hERG channel blocking activity and all are subject to practical limitations that also need to be considered prior to investing in a particular experimental approach. The approach selected, if any, should reflect the resources and expertise available. In any case, it is essential to be aware of the experimental limitations and potential inaccuracies that are inherent to each approach. This article is a commentary on Pollard , pp. 12–21 of this issue and is part of a themed section on QT safety. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2010
在药物开发中，早期识别潜在的阻断人类 ether-a-go-go 相关基因（hERG）通道的能力，或许是避免在临床试验中出现 QT 间期延长时出现失望的最佳方法。了解 hERG 阻断的潜在风险，有机会对分子进行修饰，以降低甚至消除这种非预期的活性，如果在这种修饰中没有成功，那么这就是停止该分子进一步开发的一个很好的理由。在本期的 中，Pollard 讨论了早期检测 hERG 通道阻断性的不同方法。一种有吸引力的方法是在研究的早期阶段广泛筛选分子，以检测具有这种潜在风险的化合物，并将其剔除。现在有几种方法可以提供高通量格式的 hERG 通道测试，但需要对 hERG 通道阻断活性进行直接和间接的多种读数选择，所有这些方法都受到实际限制的影响，在投资特定的实验方法之前，这些都需要加以考虑。选择的方法（如果有）应反映可用的资源和专业知识。在任何情况下，都必须意识到每种方法固有的实验限制和潜在的不准确性。本文是对 Pollard 文章的评论，见本期第 12-21 页，是关于 QT 安全性的主题部分的一部分。要查看本期内容，请访问 http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2010
