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药物发现中的自动化平面电极电生理学:QPatch在Na(v)、K(Ca)2.3和K(v)11.1通道基础特性表征及高内涵筛选中的应用实例

Automated planar electrode electrophysiology in drug discovery: examples of the use of QPatch in basic characterization and high content screening on Na(v), K(Ca)2.3, and K(v)11.1 channels.

作者信息

Korsgaard Mads P G, Strøbaek Dorte, Christophersen Palle

机构信息

NeuroSearch A/S, Pederstrupvej 93, DK 2750 Ballerup, Denmark.

出版信息

Comb Chem High Throughput Screen. 2009 Jan;12(1):51-63. doi: 10.2174/138620709787048037.

DOI:10.2174/138620709787048037
PMID:19149491
Abstract

Planar chip technology has strongly facilitated the progress towards fully automated electrophysiological systems that, in contrast to the traditional patch clamp technology, have the capability of parallel compound testing. The throughput has been increased from testing below 10 compounds per day to a realized capacity approaching high throughput levels. Many pharmaceutical companies have implemented automated planar chip electrophysiology in their drug discovery process, particularly at the levels of lead optimization, secondary screening and safety testing, whereas primary screening is generally not performed. In this review, we briefly discuss the technology and give examples from selected NeuroSearch ion channel programs, where one of the systems, the QPatch, has been evaluated for use in lead optimization and primary screening campaigns, where high information content was a requirement.

摘要

平面芯片技术极大地推动了全自动化电生理系统的发展。与传统膜片钳技术相比,该系统具备并行化合物测试的能力。通量已从每天测试不到10种化合物提高到接近高通量水平的实际测试能力。许多制药公司在其药物发现过程中采用了自动化平面芯片电生理学技术,尤其是在先导优化、二级筛选和安全性测试阶段,而一级筛选通常不采用该技术。在本综述中,我们简要讨论了这项技术,并列举了NeuroSearch公司选定的离子通道项目中的实例,其中一个系统QPatch已被评估用于先导优化和一级筛选活动,这些活动需要高信息量。

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