Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
Mol Pharmacol. 2018 Apr;93(4):266-269. doi: 10.1124/mol.117.111187. Epub 2018 Jan 18.
The question of whether signaling bias is a viable discovery strategy for drug therapy is discussed as a value proposition. On the positive side, bias is easily identified and quantified in simple in vitro functional assays with little resource expenditure. However, there are valid pharmacological reasons why these in vitro bias numbers may not accurately translate to in vivo therapeutic systems making the expectation of direct correspondence of in vitro bias to in vivo systems a problematic process. Presently, in vitro bias is used simply as a means to identify unique molecules to be advanced to more complex therapeutic assays but from this standpoint alone, the value proposition lies far to the positive. However, pharmacological attention needs to be given to the translational gap to reduce inevitable and costly attrition in biased molecule progression.
是否信号偏倚是药物治疗的一种可行的发现策略，这被作为一个价值主张进行讨论。从积极的方面来看，在体外简单的功能测定中，通过很少的资源投入就可以很容易地识别和量化偏倚。然而，有一些有效的药理学原因表明，这些体外偏倚数值可能不能准确地转化为体内治疗系统，使得体外偏倚与体内系统的直接对应预期成为一个有问题的过程。目前，体外偏倚仅仅被用作识别独特分子的手段，以推进到更复杂的治疗测定中，但从这一角度来看，其价值主张是非常积极的。然而，需要关注药理学方面的转化差距，以减少偏倚分子进展中不可避免的和昂贵的损耗。
