One of the major challenges in early drug discovery is the recognition of frequent hitters (FHs), that is, compounds that nonspecifically bind to a range of macromolecular targets or false positives caused by various types of assay interferences. In this review, we survey the mechanisms underlying different types of FHs, including aggregators, spectroscopic interference compounds (i.e., luciferase inhibitors and fluorescent compounds), chemical reactive compounds, and promiscuous compounds. We also review commonly used experimental detection techniques and computational prediction models for FH identification. In addition, the rational applications of these computational filters are discussed. It is believed that, with the rational use of FH filters, the efficiency of drug discovery will be significantly improved.

中文翻译：

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频繁击中：高通量筛选中的令人讨厌的伪影。

早期药物发现中的主要挑战之一是识别频繁使用的击打剂（FH），即那些与各种大分子靶标或由各种类型的测定干扰引起的假阳性反应非特异性结合的化合物。在这篇综述中，我们调查了不同类型的FH的潜在机制，包括聚集剂，光谱干扰化合物（即荧光素酶抑制剂和荧光化合物），化学反应性化合物和混杂化合物。我们还回顾了用于FH识别的常用实验检测技术和计算预测模型。此外，还讨论了这些计算过滤器的合理应用。相信，通过合理使用FH过滤器，药物发现的效率将大大提高。