药物相似度定量可用于筛选候选药物。定量药物相似度(QED)通常用于评估定量药物功效,但不适用于筛选针对蛋白质-蛋白质相互作用(PPI)的化合物。最近引起了人们的注意。因此,我们开发了以PPI为目标的化合物的定量估计指数(QEPPI),专门用于PPI靶向化合物的早期筛选。QEPPI是针对PPI靶向药物的QED方法的扩展,该方法基于药物/化合物的可用信息对理化性质进行建模,特别是那些报告对PPI采取行动的人。FDA批准的iPPI-DB中的药物和化合物,其中包括PPI抑制剂和稳定剂,使用QEPPI进行评估。结果表明,QEPPI比QED更适合于PPI靶向化合物的早期筛查。QEPPI也被认为是“四规则”(RO4)的扩展概念,PPI抑制剂指数。我们使用F分数和其他指标评估了QEPPI和RO4对PPI目标化合物和FDA批准的药物数据集的歧视性表现。RO4和QEPPI的F评分分别为0.451和0.501。QEPPI显示出更好的性能,并能够量化早期PPI药物发现的药物相似度。因此,它可以用作初始过滤器来有效地筛选PPI靶向化合物。
Drug-likeness quantification is useful for screening drug candidates. Quantitative estimates of drug-likeness (QED) are commonly used to assess quantitative drug efficacy but are not suitable for screening compounds targeting protein-protein interactions (PPIs), which have recently gained attention. Therefore, we developed a quantitative estimate index for compounds targeting PPIs (
QEPPI), specifically for early-stage screening of PPI-targeting compounds.
QEPPI is an extension of the QED method for PPI-targeting drugs that models physicochemical properties based on the information available for drugs/compounds, specifically those reported to act on PPIs. FDA-approved drugs and compounds in iPPI-DB, which comprise PPI inhibitors and stabilizers, were evaluated using QEPPI. The results showed that QEPPI is more suitable than QED for early screening of PPI-targeting compounds.
QEPPI was also considered an extended concept of the \"Rule-of-Four\" (RO4), a PPI inhibitor index. We evaluated the discriminatory performance of
QEPPI and RO4 for datasets of PPI-target compounds and FDA-approved drugs using F-score and other indices. The F-scores of RO4 and
QEPPI were 0.451 and 0.501, respectively. QEPPI showed better performance and enabled quantification of drug-likeness for early-stage PPI drug discovery. Hence, it can be used as an initial filter to efficiently screen PPI-targeting compounds.