| 王涛,张思琪.靶向雄激素受体的降解剂药物研究进展[J].中国海洋药物,2026,45(1):95-105. |
| 靶向雄激素受体的降解剂药物研究进展 |
| Research Progress of Degraders Targeting Androgen Receptor |
| 投稿时间：2024-05-13 修订日期：2024-08-02 |
| DOI：10.13400/j.cnki.cjmd.2026.01.013 |
| 中文关键词: 雄激素受体 前列腺癌 蛋白水解靶向嵌合体PROTAC 小分子降解剂 |
| English Keywords:androgen receptor prostate cancer proteolysis targeting chimeras PROTAC small molecule degraders |
| Fund Project: |
|
| 摘要点击次数: 1569 |
| 全文下载次数: 1 |
| 中文摘要: |
| 雄激素受体（androgen receptor，, AR）在去势抵抗性前列腺癌（castration-resistant prostate cancer，CRPC）的发生和发展中起着重要作用，然而由于AR配体结合区域发生的点突变、剪切突变等因素，导致现有抗雄激素药物逐渐产生耐药性问题。近年来，通过小分子药物诱导AR降解，为克服CRPC治疗中的耐药问题提供了新的思路。该综述围绕靶向AR的降解剂进行了概述，包括蛋白水解靶向嵌合体（proteolysis targeting chimeras，PROTACs）、选择性AR降解剂（selective androgen receptor degraders，SARDs）和其他具有机制的AR降解剂。深入了解不同AR降解剂的设计思路与作用机制，对CRPC治疗策略的未来发展具有重要意义。 |
| English Summary: |
| Androgen receptor (AR) is pivotal in the progression of castration-resistant prostate cancer (CRPC). Despite this, the emergence of resistance to current anti-androgen therapeutics is a significant clinical challenge, often attributed to point mutations and alternative splicing within the ligand-binding domain of the AR. In light of these challenges, the recent advent of small-molecule drugs capable of inducing AR degradation has presented a novel strategy to surmount resistance in CRPC treatment. This review outlines the AR-targeting degraders, including Proteolysis Targeting Chimeras (PROTACs), Selective Androgen Receptor Degraders (SARDs), and a spectrum of AR degraders that operate through diverse mechanisms. An in-deep understanding of the design concepts and mechanisms underlying these different AR degraders is of great significance for the development of CRPC. An in-deep understanding of the design concepts and mechanisms underlying these different AR degraders is of great significance for the development of CRPC therapeutic strategies. |
| 查看全文 查看/发表评论 下载PDF阅读器 |
|
| 关闭 |