雄激素受体抑制剂的研究进展  

Progress on the study of androgen receptor inhibitors

作　　者：刘波[1] 刘俊杰[2] 袁玉梅[1] 赵桂森[1] 

机构地区：[1]山东大学药学院药物化学研究所,山东济南250012 [2]山东大学海洋学院,山东威海264209

出　　处：《中国药物化学杂志》2010年第5期389-393,466,共6页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(20872082);山东省自然科学基金项目(Y2007C060)

摘　　要：雄激素受体与前列腺癌的发生、发展密切相关,它是配体依赖的转录因子,其与雄激素结合后发生构象转化形成二聚体而活化,并进入细胞核中与相应的DNA反应元件结合,促进靶基因的转录,进而促进细胞的增殖。在前列腺癌组织中,雄激素受体的增殖或突变能使其对血清中较低含量的雄激素敏感,是前列腺癌恶化的主要原因。设计合成对野生型及突变型雄激素受体具有较好抑制活性的药物是治疗前列腺癌的首要策略。该文综述了雄激素受体的结构、功能及其抑制剂的研究进展,期望为新型抗前列腺癌药物的设计研究提供参考。Androgen receptor is a DNA-binding transcription factor that belongs to a large superfamily of nuclear hormone receptors,and plays a central role in normal prostate development and in prostate cancer initiation and progression.In the cytoplasm,androgen receptor is stabilized by the binding of chaperone proteins,including heat shock protein 90（Hsp90）.Upon agonist binding to its ligand-binding domain,androgen receptor goes through a series of conformational changes and the dimeric androgen receptor translocates to the nucleus.Translocated androgen receptor then binds to specific DNA sequences through its DNA-binding domain.Coactivators and transcriptional machinery are then recruited to this protein/DNA complex to initiate gene transcription.The androgen receptor,through mutations or overamplification,may sensitive to low levels of androgens.Currently,targeting on the wild and mutant androgen receptor is a hot research point for the design and development of anti-prostate cancer drugs.In this paper,the structure and function of androgen receptor and androgen antagonists were reviewed.It is expected to help the design of new anti-prostate cancer drugs.

关 键 词：前列腺癌 雄激素受体 雄激素受体抑制剂 

分 类 号：R737.25[医药卫生—肿瘤]