Farre Cecilia, Fertig Niels
Nanion Technologies , Gabrirelenstrasse 9, 80636 München , Germany
Expert Opin Drug Discov. 2014 Oct;9(10):1103-7. doi: 10.1517/17460441.2014.942217. Epub 2014 Jul 25.
From a drug discovery point of view, ion channels are very interesting and challenging targets. Over the past decade, great efforts have been made in developing platforms for patch clamp-based high-quality screening of ion channels in discovering new drug candidates as well for evaluating their safety profiles. Indeed, the automated patch clamp (APC) has recently reached the data throughput requirements of high-throughput screening (HTS) allowing for new screening strategies with ion channel active compounds.
This editorial article comments on the past and present developments of APC-based drug screening. Furthermore, it also looks at the implications of APC technology meeting HTS-standards as well as its use in compound safety evaluation.
In the imminent future, we will see a paradigm shift in ion channel drug screening toward using APC-based platforms for primary drug library screens. This way, the redundancy of the drug discovery process and the risk of false-negatives could be drastically reduced. Furthermore, cardiac safety can be addressed early, avoiding late-phase withdrawals with promising drug candidates. It is our firm belief that APC-based ion channel HTS will facilitate the discovery of candidates, which otherwise would have not been found, and shorten the drug development cycle, saving time and cost.
从药物发现的角度来看,离子通道是非常有趣且具有挑战性的靶点。在过去十年中,人们为开发基于膜片钳的高质量离子通道筛选平台付出了巨大努力,用于发现新的药物候选物以及评估它们的安全性。事实上,自动膜片钳(APC)最近已达到高通量筛选(HTS)的数据通量要求,从而能够采用针对离子通道活性化合物的新筛选策略。
这篇社论文章评论了基于APC的药物筛选的过去和当前发展。此外,还探讨了APC技术达到HTS标准的意义及其在化合物安全性评估中的应用。
在不久的将来,我们将看到离子通道药物筛选朝着使用基于APC的平台进行主要药物库筛选的范式转变。通过这种方式,药物发现过程的冗余性和假阴性风险可以大幅降低。此外,可以尽早解决心脏安全性问题,避免有前景的药物候选物在后期被撤回。我们坚信,基于APC的离子通道HTS将有助于发现原本无法发现的候选物,并缩短药物开发周期,节省时间和成本。