Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Nat Chem. 2012 Jan 24;4(2):90-8. doi: 10.1038/nchem.1243.
Drug-likeness is a key consideration when selecting compounds during the early stages of drug discovery. However, evaluation of drug-likeness in absolute terms does not reflect adequately the whole spectrum of compound quality. More worryingly, widely used rules may inadvertently foster undesirable molecular property inflation as they permit the encroachment of rule-compliant compounds towards their boundaries. We propose a measure of drug-likeness based on the concept of desirability called the quantitative estimate of drug-likeness (QED). The empirical rationale of QED reflects the underlying distribution of molecular properties. QED is intuitive, transparent, straightforward to implement in many practical settings and allows compounds to be ranked by their relative merit. We extended the utility of QED by applying it to the problem of molecular target druggability assessment by prioritizing a large set of published bioactive compounds. The measure may also capture the abstract notion of aesthetics in medicinal chemistry.
当在药物发现的早期阶段选择化合物时，类药性是一个关键的考虑因素。然而，绝对意义上的类药性评估并不能充分反映化合物质量的全貌。更令人担忧的是，广泛使用的规则可能会无意中助长不良的分子性质膨胀，因为它们允许符合规则的化合物侵犯其边界。我们提出了一种基于可接受性概念的类药性度量方法，称为类药性定量估计（QED）。QED 的经验原理反映了分子性质的基础分布。QED 直观、透明、在许多实际环境中易于实现，并允许根据相对优点对化合物进行排序。我们通过将其应用于通过优先考虑一大组已发表的生物活性化合物来评估分子靶标可药性的问题，扩展了 QED 的实用性。该度量方法还可以捕捉药物化学中美学的抽象概念。
