Segall Matthew D, Yusof Iskander, Champness Edmund J
Optibrium Ltd. , 7221 Cambridge Research Park, Beach Drive, Cambridge CB25 9TL, U.K.
J Med Chem. 2016 May 12;59(9):4267-77. doi: 10.1021/acs.jmedchem.5b01921. Epub 2016 Mar 18.
Drug discovery is a multiparameter optimization process in which the goal of a project is to identify compounds that meet multiple property criteria required to achieve a therapeutic objective. However, once a profile of property criteria has been chosen, the impact of these criteria on the decisions made regarding progression of compounds or chemical series should be carefully considered. In some cases the decision is very sensitive to a specific property criterion, and such a criterion may artificially distort the direction of the project; any uncertainty in the "correct" value or the importance of this criterion may lead to valuable opportunities being missed. In this paper, we describe a method for analyzing the sensitivity of the prioritization of compounds to a multiparameter profile of property criteria. We show how the results can be easily interpreted and illustrate how this analysis can highlight new avenues for exploration.
药物发现是一个多参数优化过程，在这个过程中，一个项目的目标是识别出符合实现治疗目标所需的多个性质标准的化合物。然而，一旦选择了性质标准的概况，就应该仔细考虑这些标准对有关化合物或化学系列进展所做决策的影响。在某些情况下，决策对特定的性质标准非常敏感，这样的标准可能会人为地扭曲项目的方向；该标准“正确”值或重要性的任何不确定性都可能导致错过宝贵的机会。在本文中，我们描述了一种分析化合物优先级对性质标准多参数概况敏感性的方法。我们展示了结果如何能够轻松解读，并说明了这种分析如何能够突出新的探索途径。
