Nature Chemical Biology ( IF 12.9 ) Pub Date : 2021-05-25 , DOI: 10.1038/s41589-021-00768-9 Thomas Whitmarsh-Everiss 1 , Luca Laraia 1
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.
中文翻译:
靶向自噬的小分子探针
自噬涉及广泛的(病理)生理过程,包括维持细胞稳态、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量很大,因为它们能够作为更好地理解这一基本过程的工具和潜在的治疗方法。尽管该领域取得了重大进展,但在自噬特异性探针的开发和全面表征方面仍存在重大挑战。在这篇综述中,我们讨论了自噬调节小分子的最新进展,包括激活剂和抑制剂开发中面临的具体挑战,并推荐了它们的使用指南。最后,我们讨论了劫持目标蛋白质降解过程的可能性,