A Complementary Scale of Biased Agonism for Agonists with Differing Maximal Responses.
A Complementary Scale of Biased Agonism for Agonists with Differing Maximal Responses.
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DOI：
10.1038/s41598-017-15258-z
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发表时间：
2017-11-13
影响因子：
4.6
通讯作者：
Giraldo J
中科院分区：
文献类型：
--
作者：
Burgueño J;Pujol M;Monroy X;Roche D;Varela MJ;Merlos M;Giraldo J
近年来文献中令人信服的数据毫无疑问地证明了G蛋白偶联受体功能的多维性，以及一些配体可以以不同的功效与受体可以通过其传递信号的多个途径偶联的事实，这种现象通常被称为功能选择性或偏向激动。目前，基于激动作用的Black和Leff操作模型的转导系数（log（τ/KA））被广泛用于计算偏倚。然而，在单个参数中组合亲和力和功效可以导致化合物显示一种途径相对于另一种途径的定义的计算偏差，尽管显示不同的实验偏差偏好。在本文中，我们提出了一种新的尺度（log（τ）），试图给不同的化合物配置文件，以更好地分类化合物和量化他们的偏见额外的物质。疗效驱动log（τ）量表并非亲和力和疗效驱动log（τ/KA）量表的替代品，而是在存在部分激动作用的情况下作为补充。使用μ-阿片受体激动剂的理论和实践方法。
Compelling data in the literature from the recent years leave no doubt about the pluridimensional nature of G protein-coupled receptor function and the fact that some ligands can couple with different efficacies to the multiple pathways that a receptor can signal through, a phenomenon most commonly known as functional selectivity or biased agonism. Nowadays, transduction coefficients (log(τ/KA)), based on the Black and Leff operational model of agonism, are widely used to calculate bias. Nevertheless, combining both affinity and efficacy in a single parameter can result in compounds showing a defined calculated bias of one pathway over other though displaying varying experimental bias preferences. In this paper, we present a novel scale (log(τ)), that attempts to give extra substance to different compound profiles in order to better classify compounds and quantify their bias. The efficacy-driven log(τ) scale is not proposed as an alternative to the affinity&efficacy-driven log(τ/KA) scale but as a complement in those situations where partial agonism is present. Both theoretical and practical approaches using μ-opioid receptor agonists are presented.
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影响因子：
4.6
作者：
Onaran, H. Ongun;Ambrosio, Caterina;Costa, Tommaso
通讯作者：
Costa, Tommaso
DOI：
10.1124/jpet.301.3.1179
发表时间：
2002-06-01
影响因子：
3.5
作者：
Kilts, JD;Connery, HS;Mailman, RB
通讯作者：
Mailman, RB
DOI：
10.1124/jpet.108.145219
发表时间：
2009-01-01
影响因子：
3.5
作者：
Figueroa, Katherine W.;Griffin, Michael T.;Ehlert, Frederick J.
通讯作者：
Ehlert, Frederick J.
影响因子：
7.3
作者：
BLACK, JW;LEFF, P;WOOD, J
通讯作者：
WOOD, J
影响因子：
5
作者：
Kenakin, Terry;Watson, Christian;Novick, Steven
通讯作者：
Novick, Steven