Department of Chemistry, Technical University of Denmark, Kongens Lyngby, Denmark.
Nat Chem Biol. 2021 Jun;17(6):653-664. doi: 10.1038/s41589-021-00768-9. Epub 2021 May 25.
Autophagy is implicated in a wide range of (patho)physiological processes including maintenance of cellular homeostasis, neurodegenerative disorders, aging and cancer. As such, small molecule autophagy modulators are in great demand, both for their ability to act as tools to better understand this essential process and as potential therapeutics. Despite substantial advances in the field, major challenges remain in the development and comprehensive characterization of probes that are specific to autophagy. In this Review, we discuss recent developments in autophagy-modulating small molecules, including the specific challenges faced in the development of activators and inhibitors, and recommend guidelines for their use. Finally, we discuss the potential to hijack the process for targeted protein degradation, an area of great importance in chemical biology and drug discovery.
自噬参与了广泛的（病理）生理过程，包括维持细胞内环境稳定、神经退行性疾病、衰老和癌症。因此，小分子自噬调节剂的需求很大，既可以作为更好地理解这一基本过程的工具，也可以作为潜在的治疗药物。尽管该领域取得了重大进展，但在开发和全面表征特异性自噬的探针方面仍存在重大挑战。在这篇综述中，我们讨论了小分子自噬调节剂的最新进展，包括在开发激活剂和抑制剂时面临的具体挑战，并为它们的使用提出了建议。最后，我们讨论了靶向蛋白降解的可能性，这是化学生物学和药物发现领域的一个重要领域。
