Structure & Biophysics, Discovery Enabling Capabilities & Sciences, AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom.
Drug Discov Today. 2011 Nov;16(21-22):910-3. doi: 10.1016/j.drudis.2011.09.006. Epub 2011 Sep 10.
The kinetics of ligand-target interactions have been recognised as being instrumental in dictating the efficacy of drug action. Increased focus on kinetic signatures in drug discovery has concincided with improvements in label free methodology for measuring kinetic parameters. Simultaneously, focus has also been applied to increasing the quality of compounds, in terms of their physicochemical properties. To facilitate this drive towards higher compound quality, metrics such as ligand efficiency and enthalpic efficiency have been employed. We propose another metric, kinetic efficiency, that may be used pragmatically to help identify those compounds displaying differentiated kinetic behaviour. The combination of these metrics has the potential to improve decision-making in drug discovery leading to higher quality compounds and series.
配体-靶标相互作用的动力学已被认为对药物作用的疗效起着重要作用。在药物发现中对动力学特征的关注增加，同时也伴随着用于测量动力学参数的无标记方法的改进。同时，人们也关注提高化合物的质量，包括其物理化学性质。为了促进这一提高化合物质量的趋势，已经采用了一些指标，如配体效率和焓效率。我们提出了另一个指标，即动力学效率，它可以在实践中用于帮助识别那些显示出不同动力学行为的化合物。这些指标的结合有可能改善药物发现中的决策，从而得到更高质量的化合物和系列。
