Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Research Centre for Natural Sciences, Hungarian Academy of Sciences, 1117 Budapest, Magyar Tudósok körútja 2., 1525 Budapest, PO Box 17, Hungary.
Nat Rev Drug Discov. 2014 Feb;13(2):105-21. doi: 10.1038/nrd4163.
The judicious application of ligand or binding efficiency metrics, which quantify the molecular properties required to obtain binding affinity for a drug target, is gaining traction in the selection and optimization of fragments, hits and leads. Retrospective analysis of recently marketed oral drugs shows that they frequently have highly optimized ligand efficiency values for their targets. Optimizing ligand efficiency metrics based on both molecular mass and lipophilicity, when set in the context of the specific target, has the potential to ameliorate the inflation of these properties that has been observed in current medicinal chemistry practice, and to increase the quality of drug candidates.
在片段、命中和先导化合物的选择和优化中，合理应用配体或结合效率指标（定量描述获得药物靶标结合亲和力所需的分子性质）正受到越来越多的关注。最近上市的口服药物的回顾性分析表明，它们的靶标通常具有高度优化的配体效率值。基于分子质量和脂溶性优化配体效率指标，并结合特定靶标进行设置，有可能改善当前药物化学实践中观察到的这些性质的膨胀，并提高候选药物的质量。
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