Department of Life Science Informatics, Bonn-Aachen International Center for Information Technology, Rheinische Friedrich-Wilhelms-Universität Bonn, Dahlmannstr. 2, 53113, Bonn, Germany.
ChemMedChem. 2018 Mar 20;13(6):490-494. doi: 10.1002/cmdc.201700535. Epub 2017 Nov 6.
Compound promiscuity can be viewed in different ways. We distinguish "bad" promiscuity resulting from chemical liabilities, nonspecific binding, or assay artifacts, from "good" promiscuity representing true multitarget activities. Investigating multitarget activities of small molecules is scientifically stimulating and therapeutically relevant. To better understand the molecular basis of multitarget activities, structure-promiscuity relationships (SPRs) are explored. For this purpose, "promiscuity cliffs" (PCs) have been introduced, which can be rationalized as an extension of the activity cliff (AC) concept. A PC is defined as a pair of structural analogues that are active against different numbers of targets (given a difference threshold). As discussed herein PCs frequently capture surprising SPRs and encode many experimentally testable hypotheses.
化合物的混杂性可以从不同的角度来看待。我们将因化学缺陷、非特异性结合或检测误差而导致的“不良”混杂性与代表真正多靶点活性的“良好”混杂性区分开来。研究小分子的多靶点活性在科学上具有刺激性，在治疗上也有相关性。为了更好地理解多靶点活性的分子基础，正在探索结构混杂性关系 (SPR)。为此，引入了“混杂性悬崖”(PC)，可以将其合理化作为活性悬崖 (AC) 概念的延伸。PC 被定义为一对结构类似物，它们对不同数量的靶点具有活性(给定差异阈值)。如本文所述，PC 经常捕获令人惊讶的 SPR 并编码许多可通过实验检验的假说。
