Niepel Mario, Hafner Marc, Chung Mirra, Sorger Peter K
HMS LINCS Center, Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, Massachusetts.
Curr Protoc Chem Biol. 2017 Jun 19;9(2):55-74. doi: 10.1002/cpch.21.
Measuring the potencies of small-molecule drugs in cell lines is a critical aspect of preclinical pharmacology. Such experiments are also prototypical of high-throughput experiments in multi-well plates. The procedure is simple in principle, but many unrecognized factors can affect the results, potentially making data unreliable. The procedures for measuring drug response described here were developed by the NIH LINCS program to improve reproducibility. Key features include maximizing uniform cell growth during the assay period, accounting for the effects of cell density on response, and correcting sensitivity measures for differences in proliferation rates. Two related protocols are described: one involves an endpoint measure well-suited to large-scale studies and the second is a time-dependent measurement that reveals changes in response over time. The methods can be adapted to other types of plate-based experiments. © 2017 by John Wiley & Sons, Inc.
在细胞系中测定小分子药物的效力是临床前药理学的一个关键方面。此类实验也是多孔板高通量实验的典型代表。该程序原则上很简单，但许多未被认识到的因素会影响结果，可能导致数据不可靠。此处描述的测量药物反应的程序由美国国立卫生研究院（NIH）的LINCS计划开发，以提高可重复性。关键特征包括在测定期间使细胞生长最大化均匀，考虑细胞密度对反应的影响，以及针对增殖率差异校正敏感性测量。描述了两个相关方案：一个涉及适用于大规模研究的终点测量，另一个是随时间变化的测量，可揭示反应随时间的变化。这些方法可适用于其他类型的基于平板的实验。©2017约翰威立国际出版公司
