基于雄激素受体通路的PROTAC分子研究进展  

Research progress of PROTAC molecules based on androgen receptor pathway

作　　者：张心玥 史雨豪 叶宇航 陈聪 孟祥国 ZHANG Xin-yue;SHI Yu-hao;YE Yu-hang;CHEN Cong;MENG Xiang-guo(School of Health Science and Engineering USST,Shanghai 200093,China;School of Pharmacy,Shanghai University of Medicine and Health Sciences,Shanghai 201318,China;School of Pharmaceutical Engineering,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]上海理工大学健康科学与工程学院,上海200093 [2]上海健康医学院药学院,上海201318 [3]沈阳药科大学制药工程学院,辽宁沈阳110016

出　　处：《化学研究与应用》2024年第11期2465-2477,共13页Chemical Research and Application

基　　金：2021年科研骨干校外学术导师项目资助。

摘　　要：雄激素受体(androgen receptor,AR)在前列腺癌的发生和发展过程中扮演着至关重要的角色。在临床长期雄激素剥夺治疗中,AR过度表达、AR基因突变和AR剪接体等现象的出现,可能会导致雄激素受体通路再度激活,并不可避免地进展为去势抵抗性前列腺癌。蛋白降解靶向嵌合体(proteolysis targetingchimera,PROTAC)在靶向AR降解方面进展显著,针对AR的PROTAC降解剂通过促进AR降解来阻断雄激素受体信号通路,有望为前列腺癌的临床治疗带来新的突 破。本文对基于雄激素受体通路的PROTAC分子进行论述。The androgen receptor(AR)plays a crucial role in the occurrence and development of prostate cancer.During long-term clinical androgen deprivation therapy,overexpression of AR,mutations in the AR gene,and aberrant splicing of AR may lead to reactivation of the androgen receptor pathway,ultimately resulting in castration-resistant prostate cancer.Proteolysis targeting chimera(PROTAC)has shown significant advancements in selectively degrading AR.By promoting degradation of AR,PROTAC-based agents effectively block the androgen receptor signaling pathway,offering promising prospects for innovative clinical approaches towards treating prostate cancer.PROTAC molecules based on the androgen receptor pathway would be discussed in this article.

关 键 词：雄激素受体 蛋白降解靶向嵌合体 组蛋白去乙酰化酶6 前列腺癌 

分 类 号：O657.3[理学—分析化学]