Dipartimento di Scienze Farmaceutiche, Università di Pisa, Italy.
Med Res Rev. 2011 May;31(3):364-442. doi: 10.1002/med.20186.
Recent work elucidating the role that the estrogen receptor β (ERβ), a member of the nuclear receptor superfamily, plays in regulating various physiological functions has highlighted the potential of this receptor subtype as a therapeutic target for several pathologies. In fact, molecules that are able to selectively activate ERβ hold promise for the treatment of certain cancers, as well as endometriosis, inflammatory diseases including rheumatoid arthritis, and cardiovascular and CNS conditions. Nevertheless, ERβ remains a challenging target because its ligand-binding cavity is very similar to that present in ERα, and this makes it difficult to develop ligands having sufficient levels of ERβ selectivity for therapeutic use. Nevertheless, considerable advances have recently been made in developing both nonsteroidal and steroidal ERβ-selective agonists. These molecules constitute not only important tools to probe the biological effects of the selective stimulation of ERβ, but some of them appear to be agents with considerable therapeutic potential. This study provides a detailed review of selective ERβ ligands that have been developed recently. After a brief introduction to the structure and nature of the two ERs and the biology of ERβ and its isoforms, the ligands are classified on the basis of their structures and activities. Common pharmacophore elements are highlighted throughout the description of the various chemical classes analyzed, and these elements are presented in a concluding summary overview along with a discussion of potential therapeutic applications of these agents in biomedicine.
最近的研究阐明了雌激素受体β（ERβ）在调节各种生理功能中的作用，这突显了该受体亚型作为几种病理治疗靶点的潜力。事实上，能够选择性激活 ERβ 的分子有望用于治疗某些癌症、子宫内膜异位症、包括类风湿性关节炎在内的炎症性疾病，以及心血管和中枢神经系统疾病。尽管如此，ERβ仍然是一个具有挑战性的靶点，因为它的配体结合腔与 ERα 非常相似，这使得开发具有足够治疗水平 ERβ选择性的配体变得困难。尽管如此，最近在开发非甾体和甾体 ERβ 选择性激动剂方面取得了相当大的进展。这些分子不仅是探究选择性刺激 ERβ的生物学效应的重要工具，而且其中一些似乎具有相当大的治疗潜力。本研究对最近开发的选择性 ERβ 配体进行了详细的综述。在简要介绍了两种 ER 的结构和性质以及 ERβ及其异构体的生物学特性后，根据其结构和活性对配体进行了分类。在分析的各种化学类别中，突出了常见的药效团元素，这些元素在总结概述中与讨论这些药物在生物医学中的潜在治疗应用一起呈现。
