Li Ying, Qian Lihui, Yuan Junying
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 26 Qiuyue Rd, Pudong, Shanghai 201210, China.
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 26 Qiuyue Rd, Pudong, Shanghai 201210, China; Department of Cell Biology, Harvard Medical School, 240 Longwood Ave., Boston, MA 02115, United States.
Curr Opin Chem Biol. 2017 Aug;39:74-82. doi: 10.1016/j.cbpa.2017.05.007. Epub 2017 Jun 16.
The past decade has witnessed a significant expansion of our understanding about the regulated cell death mechanisms beyond apoptosis. The application of chemical biological approaches had played a major role in driving these exciting discoveries. The discovery and use of small molecule probes in cell death research has not only revealed significant insights into the regulatory mechanism of cell death but also provided new drug targets and lead drug candidates for developing therapeutics of human diseases with huge unmet need. Here, we provide an overview of small molecule modulators for necroptosis and ferroptosis, two non-apoptotic cell death mechanisms, and discuss the molecular pathways and relevant pathophysiological mechanisms revealed by the judicial applications of such small molecule probes. We suggest that the development and applications of small molecule probes for non-apoptotic cell death mechanisms provide an outstanding example showcasing the power of chemical biology in exploring novel biological mechanisms.
在过去十年中，我们对于细胞死亡机制的理解有了显著扩展，范围已超出凋亡。化学生物学方法的应用在推动这些令人兴奋的发现方面发挥了主要作用。小分子探针在细胞死亡研究中的发现与应用，不仅为细胞死亡调控机制带来了重要见解，还为开发满足巨大未满足需求的人类疾病治疗药物提供了新的药物靶点和潜在先导药物。在此，我们概述了针对坏死性凋亡和铁死亡这两种非凋亡性细胞死亡机制的小分子调节剂，并讨论了此类小分子探针的合理应用所揭示的分子途径及相关病理生理机制。我们认为，针对非凋亡性细胞死亡机制的小分子探针的开发与应用，为展示化学生物学在探索新生物机制方面的力量提供了一个杰出范例。
