Compound Management for Quantitative High-Throughput Screening.
Compound Management for Quantitative High-Throughput Screening.
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DOI：
10.1016/j.jala.2007.12.004
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发表时间：
2008-04-01
期刊：
影响因子：
--
通讯作者：
Simeonov, Anton
中科院分区：
文献类型：
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作者：
Yasgar, Adam;Shinn, Paul;Simeonov, Anton
高效和多功能的化合物管理操作对于高通量筛选(HTS)和小分子铅开发的所有下游流程的成功至关重要。员工、设备和流程不仅需要可靠，而且需要保持灵活性并做好准备，以适应范式的变化。在本报告中，我们描述了一种系统和相关流程，该系统和相关流程使NIH化学基因组中心(NCGC)能够处理用于筛选和后续目的的化合物，NCGC是NIH路线图分子图书馆倡议内最近成立的HTS和探针开发中心。我们的筛选过程被称为定量HTS(QHTS)，包括在一系列稀释度下分析完整的化合物文库，目前包含>；200,000成员，以构建完整的浓度-反应图谱。因此，NCGC的化合物管理部门的唯一任务是准备、存储、登记和跟踪384孔格式的垂直开发的板稀释系列(即板间滴定)。它们被压缩成一系列1,536孔板，并被登记以跟踪所有后续的板存储。在这里，我们详细介绍了如何选择设备以实现384孔和1,536孔格式的自动、可靠和并行的化合物操作，制备用于qHTS的板间稀释系列的协议，以及qHTS特有的过程和问题。
An efficient and versatile Compound Management operation is essential for the success of all downstream processes in high-throughput screening (HTS) and small molecule lead development. Staff, equipment, and processes need to be not only reliable, but remain flexible and prepared to incorporate paradigm changes. In the present report, we describe a system and associated processes which enable handling of compounds for both screening and follow-up purposes at the NIH Chemical Genomics Center (NCGC), a recently-established HTS and probe development center within the Molecular Libraries Initiative of the NIH Roadmap. Our screening process, termed quantitative HTS (qHTS), involves assaying the complete compound library, currently containing >200,000 members, at a series of dilutions to construct a full concentration-response profile. As such, Compound Management at the NCGC has been uniquely tasked to prepare, store, register, and track a vertically-developed plate dilution series (i.e., inter-plate titrations) in the 384-well format. These are compressed into a series of 1,536-well plates and are registered to track all subsequent plate storage. Here, we present details on the selection of equipment to enable automated, reliable and parallel compound manipulation in 384- and 1,536-well formats, protocols for preparation of inter-plate dilution series for qHTS, as well as qHTS-specific processes and issues.