Department of Life Science Informatics, b-it, LIMES Program Unit Chemical Biology & Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Endenicher Allee 19c, D-53115 Bonn, Germany.
Future Med Chem. 2019 Mar;11(5):379-394. doi: 10.4155/fmc-2018-0299. Epub 2019 Mar 19.
Activity cliffs (ACs) are formed by structurally similar compounds with large potency differences. Accordingly, ACs reveal determinants of structure-activity relationships. This makes ACs highly interesting and relevant for medicinal chemistry and chemoinformatics. So far, ACs have been defined on the basis of generally applied molecular similarity and potency difference criteria.
We present the first assessment of ACs taking target set-dependent compound potency distributions into account, leading to a new target set-dependent definition of ACs. The formation of these ACs is analyzed in detail.
Second-generation ACs are obtained on the basis of target set-dependent potency difference thresholds. Compared with generally defined ACs, target set-dependent ACs have further increased medicinal chemistry relevance.
活性悬崖（ACs）是由具有较大效力差异的结构相似化合物形成的。因此，ACs 揭示了结构-活性关系的决定因素。这使得 ACs 对药物化学和化学信息学非常有意义和相关。到目前为止，ACs 是基于普遍应用的分子相似性和效力差异标准来定义的。
我们提出了第一个考虑目标集相关化合物效力分布的 ACs 评估，从而得到了一个新的基于目标集的 ACs 定义。这些 ACs 的形成被详细分析。
基于目标集相关的效力差异阈值，获得了第二代 ACs。与一般定义的 ACs 相比，基于目标集的 ACs 具有更高的药物化学相关性。
