非甾体类雄激素受体拮抗剂的研究进展.pdfVIP

• 88 • 现代药物与临床 Drugs Clinic 第 27 卷 第 2 期 2012 年 3 月 非甾体类雄激素受体拮抗剂的研究进展 王 峰，方 浩* 山东大学 药学院，山东 济南 250000 摘 要：研究发现，雄激素受体与前列腺癌的发生存在密切关系。雄激素拮抗疗法成为临床治疗早期前列腺癌的有效手段， 近 20 年来已有多个药物上市（如氟他胺、羟基氟他胺和比卡鲁胺等），但这些经典的药物在治疗中易产生抗雄激素撤除综合 症等问题，因此其应用受到限制。目前，新近研发的非甾体类雄激素受体拮抗剂（如 RD162 、MDV3100 和 BMS-641988 ） 活性更强，正进行临床试验，并有望解决过去雄激素受体拮抗剂存在的问题。查阅国内外相关文献，对已上市药物、当前临 床研究的药物以及近年发现的小分子雄激素受体抑制剂的研究进展进行综述。 关键词：雄激素受体；非甾体类雄激素受体拮抗剂；前列腺癌 中图分类号：R977.1 文献标志码：A 文章编号：1674 - 5515(2012)02 - 0088 - 06 Research progress on non-steroidal androgen receptor antagonists WANG Feng, FANG Hao School of Pharmaceutical Sciences, Shandong University, Jinan 250000, China Abstract: The study has found that androgen receptor is closely associated with development of prostate cancer, and now, androgen antagonist therapy has become an effective way of clinical treatment for early prostate cancer. A number of drugs were launched in the past two decades such as flutamide, hydroxyl-flutamide, and bicalutamide. However, these classic drugs were easy in the anti-androgen withdrawal syndrome which limited their application in clinical. At present, the newly-developed non-steroidal androgen receptor antagonists (such as RD162, MDV3100, and BMS-641988) show more potent activity and are tested in clinical trials, which could solve the above problems to some extents. This paper summarizes the progress on the launched drugs, the current clinical studied drugs and small-molecule androgen receptor antagonists based on relevant literatures. Key words: androgen receptor; non-steroidal androgen receptor antagonists; prostate cancer 前列腺癌已成为威胁老年男性健康的重要疾 雄激素受体及其拮抗剂的相关研究为开发新型前列 病，其发病率在西方国家较高且呈逐年上升的趋势， 腺癌治疗药物提供了重要的数据支持。 而在过去发病率较低的亚洲国家，近年来患病人数 1 雄激素受体结构 增长也在加快[1-2] 。临床治疗前列腺癌常用的方法有 雄激素受体（androgen r