Proteolysis Targeting Chimeras (PROTACs) represent a significant advancement in therapeutic drug development by leveraging the ubiquitin‐proteasome system to enable targeted protein degradation, particularly impacting oncology. This review delves into the various types of PROTACs, such as peptide‐based, nucleic acid‐based, and small molecule PROTACs, each addressing distinct challenges in protein degradation. It also discusses innovative strategies like bridged PROTACs and conditional switch‐activated PROTACs, offering precise targeting of previously “undruggable” proteins. The potential of PROTACs extends beyond oncology, with ongoing research and technological advancements needed to maximize their therapeutic potential. Future progress in this field relies on interdisciplinary collaboration and the integration of advanced computational tools to open new treatment avenues across various diseases.

中文翻译：

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限制笼中靶向嵌合体的蛋白水解能力：治疗安全性的必要且重要的改进

蛋白水解靶向嵌合体 (PROTAC) 代表了治疗药物开发的重大进步，它利用泛素-蛋白酶体系统实现靶向蛋白质降解，特别是影响肿瘤学。本综述深入研究了各种类型的 PROTAC，例如基于肽的 PROTAC、基于核酸的 PROTAC 和小分子 PROTAC，每种 PROTAC 都解决了蛋白质降解中的不同挑战。它还讨论了桥接 PROTAC 和条件开关激活 PROTAC 等创新策略，提供了对以前“不可成药”蛋白质的精确靶向。 PROTAC 的潜力超出了肿瘤学范围，需要不断进行研究和技术进步来最大限度地发挥其治疗潜力。该领域的未来进展依赖于跨学科合作和先进计算工具的集成，以开辟跨各种疾病的新治疗途径。