雌激素受体α（ERα）和β（ERβ）：亚型选择性配体及临床潜力。
Estrogen receptors alpha (ERα) and beta (ERβ): subtype-selective ligands and clinical potential.
作者信息
Paterni Ilaria, Granchi Carlotta, Katzenellenbogen John A, Minutolo Filippo
机构信息
Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
Department of Chemistry, University of Illinois, 600 S. Mathews Avenue, Urbana, IL 61801, USA.
出版信息
Steroids. 2014 Nov;90:13-29. doi: 10.1016/j.steroids.2014.06.012. Epub 2014 Jun 24.
Abstract
Estrogen receptors alpha (ERα) and beta (ERβ) are nuclear transcription factors that are involved in the regulation of many complex physiological processes in humans. Modulation of these receptors by prospective therapeutic agents is currently being considered for prevention and treatment of a wide variety of pathological conditions, such as, cancer, metabolic and cardiovascular diseases, neurodegeneration, inflammation, and osteoporosis. This review provides an overview and update of compounds that have been recently reported as modulators of ERs, with a particular focus on their potential clinical applications.
摘要
雌激素受体α（ERα）和β（ERβ）是核转录因子，参与人类许多复杂生理过程的调节。目前正在考虑使用前瞻性治疗药物对这些受体进行调节，以预防和治疗多种病理状况，如癌症、代谢性疾病和心血管疾病、神经退行性变、炎症以及骨质疏松症。本综述概述并更新了最近报道的作为雌激素受体调节剂的化合物，特别关注它们的潜在临床应用。
相似文献
1
Estrogen receptors alpha (ERα) and beta (ERβ): subtype-selective ligands and clinical potential.雌激素受体α（ERα）和β（ERβ）：亚型选择性配体及临床潜力。
Steroids. 2014 Nov;90:13-29. doi: 10.1016/j.steroids.2014.06.012. Epub 2014 Jun 24.
2
Regulation of specific target genes and biological responses by estrogen receptor subtype agonists.雌激素受体亚型激动剂对特定靶基因和生物反应的调控。
Curr Opin Pharmacol. 2010 Dec;10(6):629-36. doi: 10.1016/j.coph.2010.09.009. Epub 2010 Oct 14.
3
Cell proliferation and modulation of interaction of estrogen receptors with coregulators induced by ERα and ERβ agonists.细胞增殖以及由雌激素受体α（ERα）和雌激素受体β（ERβ）激动剂诱导的雌激素受体与共调节因子相互作用的调节
J Steroid Biochem Mol Biol. 2014 Sep;143:376-85. doi: 10.1016/j.jsbmb.2014.06.002. Epub 2014 Jun 9.
4
Estrogen receptors: therapies targeted to receptor subtypes.雌激素受体：针对受体亚型的治疗方法。
Clin Pharmacol Ther. 2011 Jan;89(1):44-55. doi: 10.1038/clpt.2010.226. Epub 2010 Dec 1.
5
Design, synthesis, and biological evaluation of cyclopropyl analogues of stilbene with raloxifene side chain as subtype-selective ligands for estrogen receptor.以雷洛昔芬侧链为导向的二苯乙烯类环丙基类似物的设计、合成及对雌激素受体亚型选择性配体的生物评价。
Arch Pharm Res. 2013 Sep;36(9):1096-103. doi: 10.1007/s12272-013-0134-2. Epub 2013 Apr 24.
6
Evaluation of ligand selectivity using reporter cell lines stably expressing estrogen receptor alpha or beta.使用稳定表达雌激素受体α或β的报告细胞系评估配体选择性。
Biochem Pharmacol. 2006 May 14;71(10):1459-69. doi: 10.1016/j.bcp.2006.02.002. Epub 2006 Mar 22.
7
In vitro and in vivo molecular imaging of estrogen receptor α and β homo- and heterodimerization: exploration of new modes of receptor regulation.雌激素受体α和β同源及异源二聚化的体外和体内分子成像：受体调控新模式的探索
Mol Endocrinol. 2011 Dec;25(12):2029-40. doi: 10.1210/me.2011-1145. Epub 2011 Nov 3.
8
New scaffolds for the design of selective estrogen receptor modulators.用于设计选择性雌激素受体调节剂的新型支架
Org Biomol Chem. 2008 Oct 7;6(19):3486-96. doi: 10.1039/b806918b. Epub 2008 Aug 4.
9
Synthetic 19-nortestosterone derivatives as estrogen receptor alpha subtype-selective ligands induce similar receptor conformational changes and steroid receptor coactivator recruitment than natural estrogens.作为雌激素受体α亚型选择性配体的合成19-去甲睾酮衍生物比天然雌激素诱导相似的受体构象变化和类固醇受体共激活因子募集。
J Steroid Biochem Mol Biol. 2006 May;99(2-3):108-14. doi: 10.1016/j.jsbmb.2006.01.005. Epub 2006 Apr 17.
10
Discovery of potent ligands for estrogen receptor beta by structure-based virtual screening.基于结构的虚拟筛选发现雌激素受体β的有效配体。
J Med Chem. 2010 Jul 22;53(14):5361-5. doi: 10.1021/jm100369g.
引用本文的文献
1
Behavior of Osteoblastic Lineage Cells When in the Presence of Tamoxifen: In Vitro and In Vivo Studies on Osseointegration.成骨细胞系细胞在他莫昔芬存在时的行为：骨整合的体外和体内研究
Dent J (Basel). 2025 Aug 1;13(8):351. doi: 10.3390/dj13080351.
2
Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO.利用炔基乙烯基环丙烷与一氧化碳的[3 + 2 + 1]环加成反应对具有四氢芴酮结构的选择性雌激素受体调节剂进行形式合成。
Beilstein J Org Chem. 2025 Aug 14;21:1639-1644. doi: 10.3762/bjoc.21.127. eCollection 2025.
3
Graptophyllum pictum (Acanthaceae) relieves some hallmarks of endometriosis in an experimental model in Wistar rats.彩叶木（爵床科）可缓解Wistar大鼠实验模型中的某些子宫内膜异位症特征。
Reprod Fertil. 2025 Sep 3;6(3). doi: 10.1530/RAF-24-0084. Print 2025 Jul 1.
4
Daidzein and Genistein: Natural Phytoestrogens with Potential Applications in Hormone Replacement Therapy.大豆苷元和染料木黄酮：在激素替代疗法中具有潜在应用价值的天然植物雌激素。
Int J Mol Sci. 2025 Jul 20;26(14):6973. doi: 10.3390/ijms26146973.
5
Production of soy aglycones as an alternative estrogen via innovative synergy of commercial and novel NYO-derived enzymes.通过商业酶和新型NYO衍生酶的创新协同作用生产大豆苷元作为替代雌激素。
Food Chem X. 2025 Jul 4;29:102732. doi: 10.1016/j.fochx.2025.102732. eCollection 2025 Jul.
6
Ameliorative effects of aqueous extract on Letrozole-induced polycystic ovary syndrome in adult female rats and formulation of sesame syrup.水提取物对来曲唑诱导的成年雌性大鼠多囊卵巢综合征的改善作用及芝麻糖浆的配方
J Tradit Complement Med. 2024 Apr 16;15(4):369-379. doi: 10.1016/j.jtcme.2024.04.008. eCollection 2025 Jul.
7
Flaxseed Extracts Impact the Cellular Structure of a Keratinocyte Model for Oral Lichen Planus-A Preliminary Study.亚麻籽提取物对口腔扁平苔藓角质形成细胞模型的细胞结构的影响——一项初步研究
Int J Mol Sci. 2025 Jun 6;26(12):5462. doi: 10.3390/ijms26125462.
8
Discovery of ERα-targeting PROTACs with intrinsic fluorescence for precision theranostics of breast cancer.发现具有内在荧光的靶向雌激素受体α（ERα）的蛋白降解靶向嵌合体（PROTACs）用于乳腺癌的精准诊疗。
RSC Med Chem. 2025 May 22. doi: 10.1039/d5md00281h.
9
Effects of , Ohwi, and Extract on Vascular Endothelial Dysfunctions in Ovariectomized Rats and Molecular Mechanisms.Ohwi和提取物对去卵巢大鼠血管内皮功能障碍的影响及分子机制。
需注意，原文中“Effects of ”后面似乎有缺失内容。
Int J Mol Sci. 2025 May 14;26(10):4708. doi: 10.3390/ijms26104708.
10
Deciphering the role of classical oestrogen receptor in insulin resistance and type 2 diabetes mellitus: From molecular mechanism to clinical evidence.解读经典雌激素受体在胰岛素抵抗和2型糖尿病中的作用：从分子机制到临床证据
Bioimpacts. 2024 Aug 4;15:30378. doi: 10.34172/bi.30378. eCollection 2025.
本文引用的文献
1
Triaryl-substituted Schiff bases are high-affinity subtype-selective ligands for the estrogen receptor.三芳基取代席夫碱是雌激素受体的高亲和力亚型选择性配体。
J Med Chem. 2014 Apr 24;57(8):3532-45. doi: 10.1021/jm500268j. Epub 2014 Apr 7.
2
Aliphatic substitution of o-carboranyl phenols enhances estrogen receptor beta selectivity.邻碳硼烷苯酚的脂肪族取代增强了雌激素受体β选择性。
Chem Pharm Bull (Tokyo). 2014;62(4):386-91. doi: 10.1248/cpb.c13-00796.
3
Coumestrol treatment prevents Na+, K+ -ATPase inhibition and affords histological neuroprotection to male rats receiving cerebral global ischemia.香豆雌酚治疗可预防钠钾ATP酶抑制，并为接受全脑缺血的雄性大鼠提供组织学神经保护。
Neurol Res. 2014 Mar;36(3):198-206. doi: 10.1179/1743132813Y.0000000286.
4
Steroid signaling: ligand-binding promiscuity, molecular symmetry, and the need for gating.类固醇信号传导：配体结合的多特异性、分子对称性以及门控的必要性。
Steroids. 2014 Apr;82:14-22. doi: 10.1016/j.steroids.2014.01.002. Epub 2014 Jan 21.
5
Differential expression of estrogen receptor α, β1, and β2 in lobular and ductal breast cancer.在乳腺小叶癌和乳腺导管癌中雌激素受体 α、β1 和 β2 的差异表达。
Proc Natl Acad Sci U S A. 2014 Feb 4;111(5):1933-8. doi: 10.1073/pnas.1323719111. Epub 2014 Jan 21.
6
Mutation of the palmitoylation site of estrogen receptor α in vivo reveals tissue-specific roles for membrane versus nuclear actions.体内雌激素受体 α 棕榈酰化位点突变揭示了膜结合与核作用在组织特异性中的作用。
Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):E283-90. doi: 10.1073/pnas.1322057111. Epub 2013 Dec 26.
7
Enhanced estrogen receptor beta (ERβ) selectivity of fluorinated carborane-containing ER modulators.含氟碳硼烷的雌激素受体调节剂对雌激素受体β（ERβ）的选择性增强。
Bioorg Med Chem Lett. 2013 Dec 15;23(24):6555-8. doi: 10.1016/j.bmcl.2013.10.067. Epub 2013 Nov 7.
8
The possibility of genistein as a new direct pulp capping agent.金雀异黄素作为一种新型直接盖髓剂的可能性。
Dent Mater J. 2013;32(6):976-85. doi: 10.4012/dmj.2013-091. Epub 2013 Nov 15.
9
Erb-041, an estrogen receptor-β agonist, inhibits skin photocarcinogenesis in SKH-1 hairless mice by downregulating the WNT signaling pathway.erb-041，一种雌激素受体-β激动剂，通过下调 WNT 信号通路抑制 SKH-1 无毛小鼠的皮肤光致癌作用。
Cancer Prev Res (Phila). 2014 Feb;7(2):186-98. doi: 10.1158/1940-6207.CAPR-13-0276. Epub 2013 Nov 11.
10
Differential effects of genistein on prostate cancer cells depend on mutational status of the androgen receptor.染料木黄酮对前列腺癌细胞的影响取决于雄激素受体的突变状态。
PLoS One. 2013 Oct 22;8(10):e78479. doi: 10.1371/journal.pone.0078479. eCollection 2013.
Zotero 插件