Shao Jinning, Xie Shangzhi, Hong Shurui, Qian Linghui
Institute of Drug Metabolism and Pharmaceutical Analysis, Research Center for Clinical Pharmacy, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, 264005, China.
ChemMedChem. 2025 Mar 15;20(6):e202400866. doi: 10.1002/cmdc.202400866. Epub 2024 Dec 26.
Autophagy is an evolutionarily conserved turnover process in eukaryotes, mediating the delivery of various cellular components to lysosomes for degradation and facilitating the recycling of the breakdown products to maintain homeostasis. By harnessing this powerful autophagy-lysosomal degradation system, strategies for targeted protein degradation (TPD) have been emerging to remove specific disease-related proteins (both intracellular and cell-surface proteins) for complete elimination of their functions, bringing new insights to drug discovery. Herein, we give a brief introduction on how autophagy works followed by a focus on available small-molecule and macromolecule-based strategies for TPD mediated by autophagy.
自噬是真核生物中一种进化上保守的周转过程，介导各种细胞成分向溶酶体的转运以进行降解，并促进分解产物的再循环以维持体内平衡。通过利用这种强大的自噬 - 溶酶体降解系统，靶向蛋白质降解（TPD）策略不断涌现，以去除特定的疾病相关蛋白（包括细胞内和细胞表面蛋白），从而完全消除其功能，为药物发现带来了新的见解。在此，我们简要介绍自噬的工作原理，随后重点介绍基于小分子和大分子的自噬介导的TPD可用策略。
