Paolini Gaia V, Lyons Richard A, Laflin Philip
Chemistry, Pfizer Ltd, Sandwich, Kent, UK.
J Biomol Screen. 2010 Dec;15(10):1183-93. doi: 10.1177/1087057110384402. Epub 2010 Oct 27.
Dose-response curves, resulting in estimates of endpoints such as the IC(50), are fundamental to drug discovery. However, some estimates are more reliable than others. It is important to know just how reliable an estimate is if we want to base decisions on it or use it in further modeling. In this study, the authors propose a new measure of endpoint reliability, based on the concept of desirability first introduced by Harrington. The solution is not dependent on the application used to analyze the experimental data, provided a number of parameters to characterize the dose-response curve are available. The authors show how this score can be used as an objective and consistent measure to rank screening results, combine information from groups of experiments, and determine optimal levels of characterization of a compound's biological activity.
剂量反应曲线可得出诸如半数抑制浓度（IC₅₀）等终点指标的估计值，是药物发现的基础。然而，有些估计值比其他的更可靠。如果我们想基于某个估计值做决策或将其用于进一步建模，了解该估计值的可靠程度很重要。在本研究中，作者基于哈林顿首次提出的合意性概念，提出了一种新的终点可靠性度量方法。只要有一些用于表征剂量反应曲线的参数，该解决方案就不依赖于用于分析实验数据的应用程序。作者展示了如何将这个分数用作一种客观且一致的度量方法，来对筛选结果进行排名、整合来自多组实验的信息，以及确定化合物生物活性表征的最佳水平。
