信号转导和转录激活因子3（STAT3）被广泛认为是多种疾病，特别是肿瘤的治疗靶点。迄今为止，已有多种STAT3抑制剂进入临床试验阶段；然而，STAT3抑制剂的发展受到许多困境的阻碍。幸运的是，STAT3 降解剂代表了一种替代且有前途的阻断 STAT3 的策略，吸引了广泛的研究兴趣。在此，我们分析了STAT3降解剂的最新进展，包括蛋白水解靶向嵌合体（PROTAC）和小分子天然产物，重点关注其结构、机制和生物活性。我们讨论了开发 STAT3 降解剂的潜在机遇和挑战。希望这篇综述能够为发现有效的 STAT3 靶向药物提供见解。版权所有 © 2024 Elsevier Ltd。保留所有权利。

Signal transducer and activator of transcription 3 (STAT3) has been widely considered as a therapeutic target for various diseases, especially tumors. Thus far, several STAT3 inhibitors have been advanced to clinical trials; however, the development of STAT3 inhibitors is hindered by numerous dilemmas. Fortunately, STAT3 degraders represent an alternative and promising strategy to block STAT3, attracting extensive research interest. Here, we analyze the recent advancements of STAT3 degraders, including proteolysis targeting chimeras (PROTACs) and small-molecule natural products, focusing on their structures, mechanisms, and biological activities. We discuss the potential opportunities and challenges for developing STAT3 degraders. It is hoped that this Review will provide insights into the discovery of potent STAT3-targeting drugs.Copyright © 2024 Elsevier Ltd. All rights reserved.