Ultra-high throughput screen of two-million-member combinatorial compound collection in a miniaturized, 1536-well assay format
Ultra-high throughput screen of two-million-member combinatorial compound collection in a miniaturized, 1536-well assay format
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DOI：
10.1177/108705710000500310
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发表时间：
2000-06-01
影响因子：
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通讯作者：
Burbaum, J
中科院分区：
文献类型：
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作者：
Dunn, D;Orlowski, M;Burbaum, J
超过200万成员药典化合物收集在1536孔微量筛选测定格式的完整调查的结果报告。一个完整的技术平台，使超高通量筛选的性能在一个小型化的1536孔测定格式，已组装和使用。该平台由用于执行微体积测定的工具组成，包括测定板、液体处理器、光学成像器和数据管理软件。使用该平台设计并开发了用于抑制蛋白酶靶标的荧光筛选测定。该测定用于对药典化合物集合进行目标酶活性抑制剂的调查筛选。调查结果证明了超高通量平台在常规筛选中的成功实施。小型化形式的测定的性能与标准96孔测定的性能相当，显示出对动力学参数的相同依赖性和测量酶抑制的能力。调查筛选确定了药典化合物集合中的活性化合物类别。使用标准96孔测定法证实了这些结果。
Results of a complete survey of the more than 2-million-member Pharmacopeia compound collection in a 1536-well microvolume screening assay format are reported. A complete technology platform, enabling the performance of ultra-high throughput screening in a miniaturized 1536-well assay format, has been assembled and utilized. The platform consists of tools for performing microvolume assays, including assay plates, liquid handlers, optical imagers, and data management software. A fluorogenic screening assay for inhibition of a protease enzyme target was designed and developed using this platform. The assay was used to perform a survey screen of the Pharmacopeia compound collection for active inhibitors of the target enzyme.The results from the survey demonstrate the successful implementation of the ultra-high throughout platform for routine screening purposes. Performance of the assay in the miniaturized format is equivalent to that of a standard 96-well assay, showing the same dependence on kinetic parameters and ability to measure enzyme inhibition. The survey screen identified an active class of compounds within the Pharmacopeia compound collection. These results were confirmed using a standard 96-well assay.