Kenakin Terry
Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
Mol Pharmacol. 2017 Oct;92(4):414-424. doi: 10.1124/mol.117.108787. Epub 2017 Jul 5.
An index of agonism is described that can be used to quantify agonist receptor selectivity, bias, cell-based agonism, and the effects of receptor mutation on signaling. The parameter is derived from agonist concentration-response curves and comprises the maximal response to the agonist (max) and the EC in the form of Δlog(max/EC). This parameter is derived from equations describing agonists as positive allosteric facilitators of receptor-signaling protein interaction. A similar index is also derived to quantify the potentiating effects of positive allosteric modulators, which can be used to quantify in situ positive allosteric modulator activity in vivo. These indices lend themselves to statistical analysis and are system-independent in that the effects of the system processing of agonist response and differences in assay sensitivity and receptor expression are cancelled. The various applications of the Δlog(max/EC) scale are described for each pharmacologic application.
本文描述了一种激动作用指数，可用于量化激动剂受体选择性、偏向性、基于细胞的激动作用以及受体突变对信号传导的影响。该参数源自激动剂浓度-反应曲线，由对激动剂的最大反应（max）和以Δlog(max/EC)形式表示的EC组成。此参数源自将激动剂描述为受体信号蛋白相互作用的正变构促进剂的方程。还推导了一个类似的指数来量化正变构调节剂的增强作用，可用于量化体内原位正变构调节剂活性。这些指数便于进行统计分析，且与系统无关，因为激动剂反应的系统处理效应以及测定灵敏度和受体表达的差异被抵消。针对每种药理学应用描述了Δlog(max/EC)量表的各种应用。
