Nonapoptotic cell death is important for human health and disease. Here, we show how various tools and techniques drawn from the chemical biology field have played a central role in the discovery and characterization of nonapoptotic cell death pathways. Focusing on the example of ferroptosis, we describe how phenotypic screening, chemoproteomics, chemical genetic analysis, and other methods enabled the elucidation of this pathway. Synthetic small-molecule inducers and inhibitors of ferroptosis identified in early studies have now been leveraged to identify an even broader set of compounds that affect ferroptosis and to validate new chemical methods and probes for various ferroptosis-associated processes. A number of limitations associated with specific chemical biology tools or techniques have also emerged and must be carefully considered. Nevertheless, the study of ferroptosis provides a roadmap for how chemical biology methods may be used to discover and characterize nonapoptotic cell death mechanisms.

中文翻译：

---

使用化学生物学方法研究非凋亡细胞死亡。

非凋亡性细胞死亡对人类健康和疾病很重要。在这里，我们展示了来自化学生物学领域的各种工具和技术如何在非凋亡细胞死亡途径的发现和表征中发挥核心作用。以铁死亡为例，我们描述了表型筛选、化学蛋白质组学、化学遗传分析和其他方法如何能够阐明这一途径。在早期研究中发现的合成小分子铁死亡诱导剂和抑制剂现在已被用于鉴定更广泛的影响铁死亡的化合物，并验证用于各种铁死亡相关过程的新化学方法和探针。还出现了与特定化学生物学工具或技术相关的许多限制，必须仔细考虑。