更新于：2024-11-21

Estropipate

哌嗪雌酮硫酯

更新于：2024-11-21

概要

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-

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

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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865

项与哌嗪雌酮硫酯相关的文献（医药）

2024-12-01·International Journal of Biological Macromolecules

Evaluating the estrogen degradation potential of laccase and peroxidase from Bacillus ligniniphilus L1 through integrated computational and experimental approaches

Article

作者: Zhe, Liang ; Zhu, Daochen ; Khalid, Hafiz Rameez ; Nawaz, Muhammad Zohaib ; Haider, Syed Zeeshan ; Alghamdi, Huda Ahmad ; Mirza, Muhammad Usman

This study investigated the degradation potential of laccase and catalase-peroxidase from the extremophilic marine bacterium Bacillus ligniniphilus L1 against endogenous and synthetic estrogen compounds using an integrated computational and experimental approach. Molecular docking identified five estrogen compounds exhibiting reliable bindings with enzymes, which were then subjected to enzyme activity assays. The degradation potential of the two enzymes against five selected estrogen compounds were investigated and compared with their commercial counterparts. Laccase from L1 showed higher degradation potential against estrone (47.02 % without and 62.21 % with ABTS) compared to commercial laccase (39 % without and 54.20 % with ABTS). For estradiol valerate, commercial laccase showed a slightly higher degradation (52.47 %) than L1 laccase (49.94 %), but with ABTS, L1 laccase performed better (74.15 % vs. 68.03 %). Notably, L1 catalase-peroxidase demonstrated significantly higher degradation for all tested compounds compared to its commercial counterpart with efficiencies of 96.16 %, 89.09 %, 74.94 %, 64.91 %, and 62.80 % against estropipate, quinestrol, estradiol valerate, estriol and estrone, respectively, revealing its potential for commercial applications. Molecular dynamics simulations revealed the interaction and stability of enzyme-estrogen complexes, with MMGBSA binding energy calculations supporting experimental results. These findings highlight the usefulness of the computational approach in elucidating the molecular mechanisms underlying enzyme-mediated bioremediation of environmental contaminants.

2024-08-01·Pharmaceutical Research

Evaluation of In Vitro Metabolism- and Transporter-Based Drug Interactions with Sunscreen Active Ingredients

Article

作者: Qosa, Hisham ; Qusa, Mohammed ; Volpe, Donna A

PURPOSEThe aim of this study was to examine the ability of sunscreen active ingredients to inhibit in vitro drug metabolism via cytochrome P450 (CYP) enzymes and drug uptake transporters.METHODSMetabolism assays with human liver microsomes were conducted for CYP2C9, CYP2D6 and CYP3A4 using probe substrates warfarin, bufuralol and midazolam, respectively. Uptake transporter assays with transfected cell lines were conducted for OAT3, OCT2 and OATP1B1 with probe substrates estrone-3-sulfate, metformin and rosuvastatin, respectively. Six sunscreen active ingredients, avobenzone, enzacamene, oxybenzone, octinoxate, trolamine, and homosalate, were evaluated up to their aqueous solubility limits in the assays.RESULTSNone of the sunscreen active ingredients inhibited CYP2D6 or CYP3A4 activities in the microsomes at concentration ranges up to tenfold higher than their known clinical total plasma levels. Only enzacamene, oxybenzone and trolamine were found to be inhibitory to CYP2C9 activity with IC₅₀ values of 14.76, 22.46 and 154.7 µM, respectively. Avobenzone, enzacamene, homosalate and octinoxate were not inhibitory to the uptake transporters at the evaluated concentrations. Oxybenzone was inhibitory to OAT3 and OCT2 with IC₅₀ values of 39.93 and 42.77 µM, respectively. Trolamine also inhibited uptake in OAT3 and OCT2 transfected cells with IC₅₀ values of 448.1 and 1376 μM, respectively.CONCLUSIONSAlthough enzacamene, oxybenzone and trolamine inhibited CYP2C9 and the renal transporters OAT3 and OCT2 in vitro, their IC₅₀ values exceeded total plasma levels found in clinical studies. Therefore, it is unlikely that these sunscreen active ingredients in sunscreen products will inhibit the metabolism or transport of co-administered drugs in consumers.

2024-08-01·Clinica Chimica Acta

Sex- and age-specific reference intervals of 16 steroid metabolites quantified simultaneously by LC-MS/MS in sera from 2458 healthy subjects aged 0 to 77 years

Article

作者: Johannsen, Trine Holm ; Juul, Anders ; Aksglaede, Lise ; Petersen, Jørgen Holm ; Lund Kårhus, Line ; Andersen, Stine Ehlern ; Flück, Christa E ; Ljubicic, Marie Lindhardt ; Upners, Emmie N ; Busch, Alexander Siegfried ; Main, Katharina M ; Andersson, Anna-Maria ; Linneberg, Allan ; Fischer, Margit Bistrup ; Hagen, Casper P ; Jørgensen, Niels ; Frederiksen, Hanne

BACKGROUNDReference intervals covering the whole life span for all the metabolites in the steroid hormone biosynthesis quantified by sensitive and robust analytical methods are sparse or not existing.OBJECTIVETo develop a state-of-the-art LC-MS/MS method for simultaneous quantification of multiple steroid metabolites and to establish detailed sex- and age-specific reference intervals for 16 steroid metabolites.MATERIALS AND METHODAn isotope diluted LC-MS/MS method was developed for simultaneous quantitation of 16 steroid hormones. Serum samples from cross-sectional cohorts of healthy infants, children, adolescents, and adults aged 0.17 months to 77 years (n = 2458) were analysed.RESULTSWith this novel, specific, and sensitive LC-MS/MS method, it was possible to quantify progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, androstenedione, testosterone, dihydrotestosterone, 11-deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, and cortisone in ≥90 % of the samples, while estrone sulfate, aldosterone and dehydroepiandrosterone were quantified in 77 %, 75 % and 60 % of the samples, respectively. 21-deoxycortisol was only detectable in 2.5 % of samples from healthy subjects. Sex- and age-dependent fluctuations observed in minipuberty, puberty and adulthood including the menopausal transition were modelled. This enabled us to establish valid reference intervals from birth to late adult life for both males and females.CONCLUSIONDetailed sex- and age-specific reference intervals of multiple, simultaneously quantified steroid metabolites by a novel and specific LC-MS/MS method provides a valuable tool for clinical practice and for future research.

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.libproxy1.nus.edu.sg/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

合作

2022-06-22

·Science Daily

Hormones are linked with sleep apnea, snoring in postmenopausal women

A new study has found an association between obstructive sleep apnea risk and low estrogen and progesterone levels in women. Middle-aged women with low levels of estrogen and progesterone are more likely to snore and to report symptoms of obstructive sleep apnea, according to a new study published this week in the open-access journal PLOS ONE by Kai Triebner of University of Bergen, Norway, and colleagues. The prevalence of obstructive sleep apnea -- in which breathing stops and starts during sleep -- is known to be higher in women after menopause. However no population-based study has previously examined whether this is the result of altered sex hormone levels. In the new study, the researchers analyzed data from 774 women aged 40 to 67 in the European Community Respiratory Health Survey, conducted in seven countries between 2010 and 2012. Women in the study participated in questionnaires on their respiratory health, women's health factors, lifestyle and sleep, and gave blood samples for hormone analysis. 551 of the women in the study (71.2%) had been told they snored, and 411 of those women also reported other symptoms of sleep apnea. Among all women, a doubling of serum concentrations of estrone was associated with 19% decreased odds of snoring. A doubling of progesterone levels was associated with 9% decreased odds of snoring. Among snorers, a doubling of the concentrations of three estrogens (17β-estradiol, estrone and estrone 3-sulfate) was associated with 17% to 23% decreased odds of women having been told they breathe irregularly during sleep. A doubling of progesterone concentration, among snorers, was associated with 12% decreased odds of having woken with a choking sensation in the previous year. The authors conclude that adjusting female sex hormones might be a strategy to decrease the high prevalence and associated morbidity of obstructive sleep apnea, but say that further longitudinal studies are required to confirm the findings. The authors add: "Female sex hormones are crucial for health and disease, and especially after menopause the hormone status should be considered to develop holistic treatment strategies."

100 项与哌嗪雌酮硫酯相关的药物交易

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