Phenotypic screening has demonstrated its advantage in the discovery of first-in-class therapeutics, whereas target-based screening has showed strength for follower drugs. Owing to the unbiased nature of phenotypic screening, novel druggable proteins can be uncovered by target identification. Chemical label-free target identification methods can eliminate the functionalization step of an original bioactive compound. Herein, we summarize recent advances in the development of label-free target identification methods, which are based on changes in protein stability against proteolysis, and chemical and thermal denaturation. Owing to the increasing application of shift in thermal stability for protein analysis in live cells and tissues, we mainly focus on the cellular stability shift assay and its proteome-wide application for target identification.

中文翻译：

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通过表型筛选进行药物发现的无标记靶标识别。

表型筛选已证明其在一流疗法中的优势，而基于靶点的筛选已显示出对后续药物的优势。由于表型筛选的无偏性，可以通过靶标鉴定发现新的可药物化蛋白质。无化学标记的目标识别方法可以消除原始生物活性化合物的功能化步骤。在此，我们总结了无标签靶标识别方法的最新进展，这些方法基于蛋白质对蛋白水解的稳定性以及化学和热变性的变化。由于活细胞和组织中蛋白质分析的热稳定性变化的应用越来越广泛，我们主要关注细胞稳定性变化分析及其在蛋白质组学中的广泛应用，以进行目标识别。