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更新于：2025-05-07

Estropipate

哌嗪雌酮硫酯

更新于：2025-05-07

概要

基本信息

药物类型

小分子化药

别名

Estra-1,3,5 (10)-triene-17-one-3-yl-sulfate、Estrone 3-sulfate、Estrone bisulfate

+ [9]

靶点

作用方式

激动剂

作用机制

ERs激动剂(雌激素受体家族激动剂)

治疗领域

内分泌与代谢疾病肿瘤皮肤和肌肉骨骼疾病

在研适应症

内分泌系统疾病乳腺癌

非在研适应症-

原研机构-

在研机构

University of Toronto

非在研机构-

权益机构-

最高研发阶段批准上市

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C18H22O5S

InChIKeyJKKFKPJIXZFSSB-CBZIJGRNSA-N

CAS号481-97-0

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关联

100 项与哌嗪雌酮硫酯相关的临床结果

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100 项与哌嗪雌酮硫酯相关的转化医学

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100 项与哌嗪雌酮硫酯相关的专利（医药）

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2,562

项与哌嗪雌酮硫酯相关的文献（医药）

2025-07-01·The Journal of Steroid Biochemistry and Molecular Biology

Evaluation of the effects of estrogens on endometrial cancer cells of different grades

Article

作者: Rižner, Tea Lanišnik ; Pušić, Maja Novak ; Pavlič, Renata

Endometrial cancer (EC) is the most common gynecological malignancy in the Western world. The molecular basis and effects of various agents are frequently studied in model EC cell lines, but the most commonly used cell lines Ishikawa, HEC-1-A, RL95-2 and KLE have not been thoroughly and systematically investigated. We characterized EC cell lines of different grades by reassessing the expression of estrogen receptors ERα, ERβ, and GPER by qPCR and Western blot and investigated the effects of estrogens, estrone-sulfate, estrone and estradiol on their proliferation, migration, and clonogenicity. Estradiol promoted the proliferation of grade 1 Ishikawa EC cells and grade 2 RL95-2 cells. Estrone and estrone sulfate also stimulated the proliferation of Ishikawa, showed a tendency to increase the proliferation of HEC-1-A and RL95-2 cells, but decreased the proliferation of KLE. Estrogens had no effect on the migration and clonogenicity of these four EC cell lines, however, there was a trend toward a smaller colony area for cells incubated with higher estrogen concentrations. We have previously shown that in EC estradiol forms from inactive estrone sulfate via the sulfatase pathway. This study showed that estrogens significantly promote the proliferation of grade 1 Ishikawa EC cells, and grade 2 RL95-2 and decrease the proliferation of grade 3 KLE cells. These differences in proliferation were associated with ERα positivity of Ishikawa cells and GPER expression in other cells.

2025-06-01·Drug Metabolism and Pharmacokinetics

Exploring the effect of intracellular loop 1 genetic variants in human ABCG2 on transport activity and protein abundance

Article

作者: Sjöstedt, Noora ; Auriola, Seppo ; Vellonen, Kati-Sisko ; Bhattacharya, Madhushree ; Suominen, Laura ; Timmermans, Ritchie G M ; Vieraankivi, Marika ; Kidron, Heidi

ABCG2 (breast cancer resistance protein, BCRP), can affect drug disposition, and thus, variation in the ABCG2 gene may alter drug exposure. We studied non-synonymous naturally occurring single-nucleotide variants (SNVs) in intracellular loop 1 (ICL1), which contains a coupling helix that transmits conformational changes in the protein. Reference ABCG2, the common SNVs V12M and Q141K, and five SNVs (K453R, I456V, H457R, G462R and G462V) in ICL1 were expressed in HEK293 cells. Additionally, combinations of selected SNVs were expressed to determine if an activating substitution in ICL1 could compensate for an inactivating substitution elsewhere. Transport of Lucifer yellow, estrone sulfate and rosuvastatin was studied using membrane vesicles and the ABCG2 abundance was quantified. While K453R and I456V abundance was similar to the reference ABCG2, abundance was lower for H457R and G462R/V. Apparent transport activities were partially substrate dependent, but excluding G462R/V, the ICL variants transported at least one of the substrates similarly to the reference ABCG2. In double substitutions, I456V had a more consistent effect than H457R on both transport activity and protein abundance. Altogether, SNVs in ICL1 can have both detrimental and beneficial effects on ABCG2 activity. Effects may be hard to predict, especially if more than one SNV is present.

2025-06-01·Journal of Pharmaceutical Sciences

In vitro characterization of SLCO2B1 genetic variants

Article

作者: Miinalainen, Annika ; Kivioja, Saara ; Niemi, Mikko ; Sinokki, Alli ; Kidron, Heidi ; Auriola, Seppo ; Bhattacharya, Madhushree ; Kiander, Wilma ; Huttunen, Kristiina M ; Vellonen, Kati-Sisko ; Gynther, Mikko

OATP2B1, encoded by SLCO2B1, is a drug transporter expressed widely throughout the body in tissues such as the intestine and liver. Genetic variation of this transporter may lead to altered disposition of OATP2B1 substrate drugs, but especially the effects of rare variants are poorly understood. The aim of this study was to characterize the effects of naturally occurring missense single nucleotide variants of SLCO2B1 (c.601G>A, c.935G>A, c.953C>T, c.1175C>, c.1457C>T, c.1559G>C, c.1596C>A, and the c.601G>A + c.935G>A haplotype) on the in vitro functionality of OATP2B1. To characterize transport activity, cellular uptake of dibromofluorescein, 5-carboxyfluorescein, estrone sulfate, and rosuvastatin was compared in OATP2B1 reference- and variant-expressing HEK293 cells. The abundance of OATP2B1 variants in HEK293 crude membrane preparations was quantified with LC-MS/MS-based quantitative targeted absolute proteomics analysis. Variant c.1559G>C impaired OATP2B1-mediated uptake of all tested substrates almost completely, but protein abundance was not reduced to the same extent. Other studied variants had comparable or only modestly reduced protein abundance and transport function compared to reference OATP2B1. These results can be utilized to understand findings from clinical pharmacogenetic studies. More importantly, the results can aid in predicting the consequences of rare variants, such as the loss-of-function variant c.1559G>C, which can be difficult to detect in clinical studies.

项与哌嗪雌酮硫酯相关的新闻（医药）

2022-06-30

·药明康德

治疗不足现象突出！《自然》子刊综述：女性进入这个关键年龄段，如何合理应用激素治疗?

▎药明康德内容团队编辑绝大多数经历绝经期的女性都会面临令人烦恼的雌激素缺乏症状，绝经期雌激素水平的下降会引起女性身体无症状的生物学变化，并且增加非传染性疾病，如心血管疾病、2型糖尿病、骨质疏松、特定类型癌症以及抑郁症的发病风险。值得一提的是，提早绝经的女性这些疾病发生的风险更高。近日，《自然》子刊 Nature Reviews Endocrinology 发表重磅综述，围绕绝经的短期和远期影响、绝经相关症状治疗适应症以及绝经潜在治疗药物进行详细阐述。论文强调，对于有症状的绝经期女性，雌激素仍然是最有效的治疗方法。绝经激素疗法（MHT）不仅可以预防骨质流失以及骨折，如果在绝经期早期开始使用，还可用于预防心脏代谢疾病的发生。截图来源： Nature Reviews Endocrinology 绝经的短期和远期影响女性一生中需要经历很多个生理阶段，其中绝经期是女性从生育年龄过渡到老年的阶段。绝经后女性卵巢的功能基本消失，这一过程可能自然发生（自然绝经）或基于医源性因素发生（继发性闭经）。目前在全球范围内，女性自然绝经的平均年龄为48.8岁，不同地区女性自然绝经年龄差异较小。女性绝经年龄对晚年健康具有重要影响。提早绝经与乳腺癌的发病风险降低有关，但是会增加卵巢早衰相关骨质疏松、心血管疾病和过早死亡的风险。绝经雌激素水平的下降会诱导衰弱性症状的产生，如血管舒缩症状（如潮热、盗汗）、焦虑、抑郁、泌尿生殖道萎缩、性功能障碍。此外，绝经后雌激素的缺乏也可能带来长期不良反应，其中最值得关注的包括骨质流失（骨折风险增加）、中心性（腹型）肥胖（增加心血管疾病发病风险）、2型糖尿病（T2DM）以及部分类型癌症的发病风险增加。目前最常报告的绝经期症状包括血管舒缩症状、睡眠障碍、情绪变化、关节痛、肌痛、泌尿生殖道萎缩、认知功能改变和体重增加。论文强调，绝大多数女性在45岁至55岁之间绝经，其中高达75%会出现雌激素缺乏相关症状。尽管目前临床上拥有安全的激素与非激素治疗手段，但是绝大多数伴有绝经症状的女性并未接受有效的、基于充足证据的获批治疗方法。绝经人群需要接受治疗的指征论文强调，雌激素水平下降将导致全身脂肪组织的增加和重新分布（内脏脂肪的比例增高），从而提高绝经人群心血管疾病、2型糖尿病、乳腺癌、子宫癌和结直肠癌的发病风险。由于绝经相关主要症状以及后遗症主要由于卵巢雌激素分泌减少所致，因此，基于雌激素、雌激素样化合物的绝经激素治疗（MHT）有望改善绝经期症状，并同时预防绝经期相关骨质流失、心脏代谢不良变化。 ▲雌激素水平变化对心脏代谢影响的可能途径（图片来源：参考资料[1]）绝经激素治疗最初的适应症包括绝经期症状的治疗以及绝经后女性（具有较高骨折风险）骨质疏松的预防。目前绝经激素治疗的适应症主要为绝经期血管舒缩症状。论文强调，女性绝经症状受到个人健康、社会心理、经济环境等多方面因素的影响，因此需考虑配合其他手段进行综合护理，如优化生活方式（如提高膳食营养、体能锻炼水平，减少饮酒和戒烟）、治疗慢性疾病相关的风险因素。绝经人群的治疗选择论文强调，绝经激素治疗（如使用药物替勃龙）是目前绝经相关症状最有效的治疗手段。在骨密度正常、骨量减少和骨质疏松的女性中，研究证实绝经激素治疗可显著降低受试者髋关节、椎体和其他骨质疏松相关骨折的风险。此外，对于常见的绝经相关泌尿生殖道萎缩，激素治疗结合非激素治疗手段也可为这部分人群带来积极获益。目前获批的绝经人群全身性激素治疗药物包括：雌激素类：结合型孕马雌激素（CEE）、微粉化17-β雌二醇、戊酸雌二醇、雌酮硫酸酯哌嗪、17-β雌二醇经皮吸收制剂、皮下埋植雌二醇、雌二醇凝胶、雌二醇半水合物凝胶；孕激素类：微粉化黄体酮、地屈孕酮、屈螺酮、醋酸炔诺酮、醋酸甲羟孕酮、左炔诺孕酮宫内节育系统；其他类型：替勃龙、共轭雌激素/巴多昔芬。对于不同类型的绝经人群，绝经激素治疗方案不同，具体而言对于接受子宫切除术的女性，应仅以最低有效剂量处方雌激素；对于保留子宫的女性，考虑到长期使用单一雌激素疗法可能会增加子宫内膜增生的发生风险，因此推荐雌激素治疗需与孕激素联合使用。此外，绝经期症状的非激素干预措施包括生活方式和饮食调整、非激素类药物、行为和替代疗法。但是，目前尚缺乏令人信服的证据证实，运动、营养补充剂或富含植物雌激素的饮食可有效缓解绝经相关症状，如血管舒缩症状。不过，越来越多的临床试验和荟萃分析的证据显示，特定抗抑郁药，如文拉法辛、帕罗西汀等，或可有效缓解绝经期血管舒缩症状。论文也强调，认知行为治疗有助于减少血管舒缩症状带来的影响，并可能对绝经期人群睡眠和情绪有额外益处。相关阅读《柳叶刀》子刊：乳腺癌5年复发风险进一步降低约32%，芳香化酶抑制剂对绝经前患者同样有效！《柳叶刀》专题：影响女性1/3生命，这个关键时期要保护心脏代谢健康为什么女性更多得甲状腺疾病？ JAMA 详述女性一生中的生理变化影响参考资料 [1] Davis, S.R., Baber, R.J. Treating menopause — MHT and beyond. Nat Rev Endocrinol (2022). https://doi.org/10.1038/s41574-022-00685-4 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医学新视点」微信公众号留言联系。如有其他合作需求，请联系wuxi_media@wuxiapptec.com