曲洛司坦(Trilostane) - 药物靶点：ERβ_在研适应症：库欣综合征，醛固酮增多症_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Abetafen、Modrastane、Modrefen

+ [9]

靶点

ERβ

作用机制

ERβ调节剂(雌激素受体β调节剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

Mochida Pharmaceutical Co., Ltd.

非在研机构

Genzyme Corp.

Bioenvision, Inc.

最高研发阶段批准上市

首次获批日期

美国 (1984-12-31),

前列腺癌

最高研发阶段(中国)-

特殊审评-

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结构

分子式C20H27NO3

InChIKeyKVJXBPDAXMEYOA-CXANFOAXSA-N

CAS号13647-35-3

关联

3

项与曲洛司坦相关的临床试验

NCT01615211 / Terminated临床2期

A Randomized Pilot Study of Two New Drug Combinations Fot the Termination fo Early Pregnancy

In menstruation an effective shedding of the endometrial lining occurs. Both progesterone and estrogen levels fall sharply at this time. During medical abortion the endometrial shedding is sometimes ineffective causing an incomplete abortion which may cause prolonged bleeding or require surgical intervention. In medical abortion a progesterone antagonist is used as treatment but the estrogen levels are not targeted. The investigators wish to explore whether addition of letrozole or trilostane which target estrogen levels can lead to a more effective shedding of the endometrial lining.

开始日期2012-05-01

申办/合作机构

Karolinska Institutet

[+2]

EUCTR2004-004533-34-GB / Not yet recruiting临床4期

A Phase IV Non-randomised Study of Modrenal® (Trilostane) in Post-menopausal Women with Advanced, Oestrogen Receptor Positive Breast Cancer for whom Prior Endocrine Therapies have Failed, One of which was an Aromatase Inhibitor

开始日期2005-05-19

申办/合作机构

Bioenvision, Inc.

NCT00181597 / Completed临床2期

A Phase II Study of Trilostane for Androgen-Independent Prostate Cancer

The main purpose of this study is to test the safety of trilostane by looking at what effects, good and bad, it has on patients with androgen-independent prostate cancer.

开始日期2004-03-01

申办/合作机构

Genzyme Corp.

100 项与曲洛司坦相关的临床结果

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100 项与曲洛司坦相关的转化医学

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100 项与曲洛司坦相关的专利（医药）

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469

项与曲洛司坦相关的文献（医药）

2025-01-01·Journal of Ethnopharmacology

Multi-omics and bioinformatics for the investigation of therapeutic mechanism of roucongrong pill against postmenopausal osteoporosis

Article

作者: Guo, Junpeng ; Li, Chenhao ; Su, Xin ; Jiang, Tao ; Meng, Qianting ; Hu, Wanli ; Guo, Jiurui ; Zhu, Xiaojuan ; Song, Wu ; Du, Xingchen ; Li, Yufen

ETHNOPHARMACOLOGICAL RELEVANCEThe Roucongrong Pill (RCRP), originating from the historical General Medical Collection of Royal Benevolence, is frequently used to treat postmenopausal osteoporosis (PMOP). Despite its prevalent application, the specific anti-osteoporotic mechanisms of RCRP remain to be elucidated.AIM OF THE STUDYThis study aims to elucidate the therapeutic mechanism of RCRP in the context of ovariectomy (OVX)-induced PMOP in rats. By employing an integrative approach, the research combines medicinal chemistry, gut microbiota (GM) profiling, metabolomics, MetOrigin traceability, network pharmacology, molecular docking, and molecular dynamics simulations to deliver a comprehensive analysis.MATERIALS AND METHODSSprague-Dawley (SD) rats underwent bilateral OVX to establish a PMOP model. The therapeutic efficacy of RCRP was evaluated through bone metrics (BMD, bone strength, BV/TV, Tb.Sp), hematoxylin and eosin (H&E) histological assessment, and bone metabolism markers (OPG, BALP, TRACP-5b, β-CTX, RANKL). Fecal metabolomics and 16S rDNA sequencing were employed to assess the influence of RCRP on GM and metabolite profiles. Furthermore, MetOrigin facilitated the traceability analysis of relevant metabolites. Molecular docking identified potential RCRP compounds with anti-PMOP activity, while their stability and protein interactions were assessed through molecular dynamics simulations. Network pharmacology further confirms the targets of action.RESULTSRCRP alleviated PMOP in rats, enhancing bone strength, cortical and trabecular BMD, BV/TV, and serum OPG levels, while reducing Tb.Sp, serum BALP, TRACP-5b, β-CTX, and RANKL concentrations. A total of twenty-six distinct metabolites were identified, of which ten-tribufos, sulfoacetic acid, betamethasone dipropionate, 9-oxooctadeca-10,12,15-trienoic acid, menatetrenone, piperlongumine, maltopentaose, enol-phenylpyruvate, catechol, pentaacetate, and (+)-2-methylpropanoic acid-exhibited correlations with six GM species: Turicibacter, Roseburia, Colidextribacter, Helicobacter, Odoribacter, and Lachnoclostridium, as determined by Spearman's correlation analysis. Notably, MetOrigin revealed the microbial metabolism of taurine and hypotaurine, along with host-specific steroid hormone synthesis. Computational docking studies demonstrated robust interactions between five RCRP-derived steroids (hydroxyecdysone, corticosterone, trilostane, 5α-androstan-3,6,17-trione, and cortisol) and key enzymes (estradiol 17α-dehydrogenase and UDP-glucuronosyltransferase), suggesting a potential enhancement of therapeutic efficacy against PMOP. Furthermore, molecular dynamics simulations indicated stable interactions between hydroxyecdysone and two proteins, with binding free energies of -67.427 kJ/mol and -156.948 kJ/mol, respectively. Through network pharmacology and molecular docking approaches, potential targets of these metabolites were identified, including estrogen receptors ESR1 and ESR2, dual specificity phosphatase 6 (DUSP6), sex hormone-binding globulin (SHBG), prostaglandin E receptor 4 (PTGER4), cannabinoid receptor 2 (CNR2), cathepsin K (CTSK), and androgen receptor (AR).CONCLUSIONSRCRP effectively mitigates OVX-induced bone loss in PMOP rats by modulating GM and associated metabolites, along with their potential targets and key metabolic pathways, including taurine and hypotaurine metabolism, as well as steroid hormone biosynthesis. These findings offer new insights into the therapeutic mechanisms by which RCRP may alleviate PMOP.

2024-10-01·Domestic Animal Endocrinology

Association between post-ACTH cortisol and trilostane dosage in dogs with pituitary-dependent hypercortisolism

Article

作者: Vargas, Alessandra Martins ; Borin-Crivellenti, Sofia ; Reis, Natani Silva ; Gouvêa, Fernanda Nastri ; Crivellenti, Leandro Zuccolotto ; Guimarães, Ednaldo Carvalho ; Pennacchi, Caio Santos ; de Cerqueira, Hévila Dutra Barbosa ; Branco, Luana de Oliveira

Trilostane is the current treatment of choice for managing pituitary-dependent hypercortisolism (PDH) in dogs. While prescribing higher initial doses may elevate the risk of iatrogenic hypocortisolism, opting for more conservative approach could result in delayed disease control, since most individuals end up requiring dosage increases. The adrenocorticotrophin stimulation test (ACTHst), a widely recognized hormonal test for assessing adrenal function, is an essential tool for monitoring the pharmacological treatment of canine hypercortisolism (CH) that can also be used for diagnostic purposes. The aim of this study was to investigate the relationship between post-ACTH cortisol (cpACTH) at PDH diagnosis and the required trilostane dose for sign control and endogenous cortisol regulation in dogs, considering a hypothesis that higher serum cpACTH concentration would necessitate a higher trilostane dosage for disease management. Data for 43 dogs with PDH had their diagnostic cpACTH recorded and correlated to the trilostane dosage necessary to control clinical signs and achieve satisfactory cortisol levels (ideally 2-7 μg/dL). The odds ratio (p=0.042) suggests that dogs with cpACTH ≥ 27 μg/dL at diagnosis are 96% more likely to need a higher trilostane dosage for achieving satisfactory control of PDH. Thus, cpACTH was found to be associated with the final trilostane dose for controlling PDH in dogs.

2024-09-01·Veterinary Medicine and Science

Successful laparotomic ethanol ablation for an adrenal tumour in a dog

Article

作者: Furusato, Shimon ; Tsuyama, Yu ; Tamura, Yu ; Kondo, Eriko

AbstractAdrenalectomy is the gold standard for canine adrenal tumours, but not always recommended due to patient age, underlying conditions and perioperative mortality. Ethanol ablation is an alternative in human medicine for poor surgical candidates. A 13‐year‐old neutered female toy‐poodle with hypercortisolism presented with severe haematuria. Ultrasonography revealed left adrenal and right kidney tumours. Due to high surgical risk, simultaneous laparotomic right nephroureterectomy and ethanol ablation of the left adrenal tumour were performed. Post‐ethanol injection complications included transient hypertension and arrhythmia, which resolved spontaneously. The adrenal tumour size decreased within 2.5 months, and cortisol levels normalised within 8 days, remaining stable for 12 months. No hypercortisolism signs were observed without trilostane until death from renal insufficiency. Autopsy showed that the ablated left adrenal gland was an adrenocortical tumour and had shrunk. Ethanol ablation may be a feasible alternative to adrenalectomy for high‐risk canine patients.

100 项与曲洛司坦相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01180	曲洛司坦	H02CA01	DB01108

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
库欣综合征	日本	Mochida Pharmaceutical Co., Ltd.	1986-02-03
醛固酮增多症	日本	Mochida Pharmaceutical Co., Ltd.	1986-02-03

未上市

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适应症	最高研发状态	国家/地区	公司	日期
前列腺腺癌	临床前	美国	Genzyme Corp.	2004-03-01
去势抵抗性前列腺癌	临床前	美国	Genzyme Corp.	2004-03-01

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASCO2004	N/A	晚期乳腺癌	714	Trilostane	(醖繭艱構鑰願範淵繭網) = 衊選夢簾憲糧糧鬱齋壓鏇築繭遞鹹夢願網淵醖 (積糧鏇憲壓選蓋構窪製 ) 更多	-	2004-07-15