hERG automated electrophysiological assays using high throughput IonWorks Barracuda primary and high

• 作 者: XueQin Chen JinFeng Yue ZhaoBing Gao
• 机 构: CAS Key Laboratory of Receptor Research,State Key Laboratory of Drug Research,Shanghai Institute of
• 出 处: 第九届海内外华人神经科学家研讨会(The 9th Symposium for Chinese Neuroscientis
• 发表日期: 2016年3期
• 关键词: hERG potassium channel drug induced LQTs automated patch clamp

　　Drug-induced prolongation of the QT interval via block of cardiac ion channel coded by human ether-à-gogo-related gene(hERG,alternative nomenclature KCNH2)is a major safety concern in the process of drug discovery and development.The advent of automated electrophysiology systems such as IonWorks Barracud(Molecular Devices,USA)and Qpatch(Sophion,Denmark)has enabled the detection of hERG blockade earlier in drug discovery.In this present work,a US drug collection of 1280 compounds were tested for hERG activity at 10 μM single dose using IonWorks Barracuda.The results showed that 79 drugs have an inhibition percentage of more than 80%on hERG at 10μM and most of them(21.5%,17/79)were antihistamine drugs including astemizole and terfenadine,which are well-known typical hERG blockers.Next concentration-response curves of the 17 antihistamine drugs were tested using Qpatch.Astemizole and terfenadine inhibited hERG currents with IC50 values of 30 nM and 240 nM,respectively.In summary,using automated electrophysiology platforms of IonWorks Barracuda and Qpatch,our work provides an efficient route to estimate potential hERG blockade of drug candidate on a large scale at early status of their discovery and development process.