Gini Coefficients as a Single Value Metric to Define Chemical Probe Selectivity

Selectivity is a
key requirement of high-quality chemical probes
and lead medicines; however, methods to quantify and compare the selectivity
of small molecules have not been standardized across the field. Herein,
we discuss the origins and use of a comprehensive, single value term
to quantify selectivity, the Gini coefficient. Case studies presented
include compounds that target protein kinases, small molecules that
bind RNA structures, and small molecule chimeras that bind to and
degrade the target RNA. With an increasing number of transcriptome-
and proteome-wide studies, we submit that reporting Gini coefficients
as a quantitative descriptor of selectivity should be used broadly.

选择性是高质量化学探针及先导药物的关键要求；然而，量化及比较小分子选择性之方法尚未在整个领域实现标准化。本文将探讨用于量化选择性之全面且单一值术语——基尼系数的起源及其应用。所提供的案例研究包括针对蛋白激酶的化合物、结合RNA结构的微小分子，以及能够结合并降解靶RNA的小分子嵌合体。随着转录组学和蛋白质组学研究的不断增多，我们认为广泛采用基尼系数作为选择性量化描述符的做法应得到推广。