靶向核受体的抗前列腺癌小分子药物研发新进展  

Recent Development in Nuclear Receptor-Targeted Small Molecule Drugs against Prostate Cancer

作　　者：袁乐儿 廖金标 蔡吕涛 胡陈娴 杨号东 盛荣[1,2] YUAN Leer;LIAO Jinbiao;CAI-LYU Tao;HU-CHEN Xian;YANG Haodong;SHENG Rong(College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China;Jinhua Institute,Zhejiang University,Jinhua 321002,China)

机构地区：[1]浙江大学药学院,浙江杭州310058 [2]浙江大学金华研究院,浙江金华321002

出　　处：《药学进展》2023年第8期578-592,共15页Progress in Pharmaceutical Sciences

基　　金：浙江省科技厅“领雁”研发攻关计划(No.2023C03110)。

摘　　要：作为全球男性第二大常见癌症,前列腺癌严重威胁着人类健康。在前列腺癌发病过程中,雄激素受体(androgen receptor,AR)起着关键作用,糖皮质激素受体(glucocorticoid receptor,GR)也参与调节部分AR通路下游基因,因此,阻断AR和GR信号通路是前列腺癌治疗的重要策略。综述从核受体AR和GR的结构特征和生物学功能出发,从药物化学角度系统介绍了近5年来靶向核受体的抗前列腺癌药物研发新进展,包括雄激素竞争性AR拮抗剂、雄激素非竞争性AR拮抗剂、AR降解剂、GR拮抗剂和AR/GR双重拮抗剂等,为去势抵抗性前列腺癌的治疗提供新思路。Prostate cancer,the second most common cancer in men worldwide,causes a serious threat to human health.Notably,the androgen receptor(AR)plays a crucial role in the pathogenesis of prostate cancer,and the glucocorticoid receptor(GR)modulates downstream genes in certain AR signaling pathways.Thus,disrupting the AR and GR signaling pathways holds great promise for effective treatment of prostate cancer.This review provides a comprehensive overview of the structural characteristics and biological functions of AR and GR,and a systematic introduction to the recent breakthroughs in medicinal chemistry for prostate cancer treatment,including the development of novel androgen competitive AR antagonists,androgen non-competitive AR antagonists,AR degraders,GR antagonists and AR/GR dual antagonists,which offer novel insight for the treatment of castration-resistant prostate cancer.

关 键 词：前列腺癌 雄激素受体拮抗剂 雄激素受体降解剂 糖皮质激素受体拮抗剂 雄激素受体/糖皮质激素受体双重拮抗剂 

分 类 号：R914.2[医药卫生—药物化学] R979.1[医药卫生—药学]