醋酸特拉司酮(Telapristone Acetate) - 药物靶点：PR_专利_临床

概要

基本信息

药物类型

小分子化药

别名

17alpha-Acetoxy-11beta-(4-(dimethylamino)phenyl)-21-methoxy-19-norpregna-4,9-dien-3,20-dione、Proellex、Proellex-V

+ [6]

靶点

PR

作用机制

PR拮抗剂(孕激素受体拮抗剂)

治疗领域

肿瘤血液及淋巴系统疾病皮肤和肌肉骨骼疾病+ [3]

在研适应症-

非在研适应症

闭经贫血乳腺癌+ [7]

原研机构

National Institutes of Health

在研机构-

非在研机构

Repros Therapeutics, Inc.

Chemical Works of Gedeon Richter Plc

National Cancer Institute

+ [2]

最高研发阶段终止临床3期

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C31H39NO5

InChIKeyJVBGZFRPTRKSBB-MJBQOYBXSA-N

CAS号198414-31-2

关联

36

项与醋酸特拉司酮相关的临床试验

NCT02811159

/ Terminated临床2期

An Open-Label Extension Study of 12 mg Proellex® (Telapristone Acetate) Administered Orally in the Treatment of Premenopausal Women With Confirmed Symptomatic Uterine Fibroids

To determine the safety of extended treatment with Proellex® in women who have successfully completed either study ZPV-201 [NCT02323646] or ZPU-203 [NCT02301897] and meet eligibility criteria.

开始日期2016-07-26

申办/合作机构

Repros Therapeutics, Inc.

NCT02314156

/ Completed临床2期IIT

Intra-mammary Distribution of Transdermal Telapristone Versus Oral Telapristone: A Randomized Window Trial in Women Undergoing Mastectomy

This randomized trial studies transdermal or oral telapristone acetate in treating patients undergoing surgery to remove the breast (mastectomy). Telapristone acetate may help prevent breast cancer from forming in premenopausal women. Giving telapristone acetate transdermally may be safer and have fewer side effects than oral administration.

开始日期2015-10-01

申办/合作机构

Northwestern University

[+1]

NCT02301897

/ Completed临床2期

A Phase 2, Multi-Center, Parallel Design, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of 6 and 12 mg Proellex® (Telapristone Acetate) Administered Orally in the Treatment of Premenopausal Women With Confirmed Symptomatic Uterine Fibroids

The primary objective of this study is to determine the safety and efficacy of two oral doses of Proellex administered for up to 2 courses of treatment (18 weeks each), each separated by an Off-Drug Interval (ODI), to premenopausal women with symptomatic uterine fibroids.

开始日期2015-03-16

申办/合作机构

Repros Therapeutics, Inc.

100 项与醋酸特拉司酮相关的临床结果

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100 项与醋酸特拉司酮相关的转化医学

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100 项与醋酸特拉司酮相关的专利（医药）

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53

项与醋酸特拉司酮相关的文献（医药）

2024-12-01·Current Medicinal Chemistry

Development and Validation of the Diagnostic Model of 7 Gene in Endometriosis

Article

作者: Zhu, Ruofei ; Liu, Yaqiong ; Lv, Zi ; Xiong, Jian ; Shi, Kun ; Zhou, Jie

Aims:To explore the diagnostic biomarkers for diagnosing endometriosis.Background:Endometriosis is a benign, progressive, estrogen-dependent gynecological disorder that has highly variant prevalence. Therefore, it is essential to develop reliable diagnostic biomarkers for endometriosis diagnosis.Objective:To explore the diagnostic biomarkers for endometriosis diagnosis.Methods:Based on transcriptome data from GSE145701, we identified potential therapeutic targets through the intersection of endometriosis-related genes from weighted gene correlation network analysis (WGCNA) and differential expression analysis. Aprotein-protein interaction (PPI) was constructed. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed for functional enrichment analysis. The intersection of hub genes from topological analysis and module genes from module-based network analysis were selected as core targets, which were used for diagnostic model construction. Its robustness was validated using GSE7305 and GSE134056. Associations of core targets with immune characteristics and pathways were further evaluated. Molecular docking was employed to evaluate the docking affinity between core targets and drugs. Additionally, western blot and quantitative real-time polymerase chain reaction were also carried out to validate molecular docking results.Results:A diagnostic model was constructed using 7 core targets, which had a high diagnostic ability for endometriosis. CTSK was positively correlated with immune scores, while CDH2 was negatively correlated with immune scores. CTSK, HGF, and EPCAM were positively correlated with energy metabolism and inflammation-related pathways, while RUNX2, FN1, NCAM1, and CDH2 were positively correlated with epithelial-to-mesenchymal transition (EMT) and unfolded protein response (UPR). Moreover, FN1 had good docking affinity with Elagolix, Esmya, and Proellex. NCAM1 might be a promising target modulated by Elagolix. In vitro experiment revealed that the expression of FN1 in human normal endometrial cell lines (hEEC) gradually decreased with the increase of Esmya concentration, indicating that FN1 was a target for Esmya.Conclusion:These results may facilitate the in-depth understanding of the development of endometriosis, and guide early diagnostic as well as clinical treatments for patients with endometriosis.

2021-12-01·Breast Cancer Research1区 · 医学

Progesterone receptor antagonists reverse stem cell expansion and the paracrine effectors of progesterone action in the mouse mammary gland

1区 · 医学

ArticleOA

作者: Yadav, Shivangi ; Kim, J Julie ; Cottone, Gannon ; Spike, Benjamin T ; Chatterton, Robert ; Ranjan, Manish ; Zeng, Zexian ; Khan, Seema A ; Clare, Susan E ; Lee, Oukseub ; Mirzaei Mehrabad, Elnaz

AbstractBackgroundThe ovarian hormones estrogen and progesterone (EP) are implicated in breast cancer causation. A specific consequence of progesterone exposure is the expansion of the mammary stem cell (MSC) and luminal progenitor (LP) compartments. We hypothesized that this effect, and its molecular facilitators, could be abrogated by progesterone receptor (PR) antagonists administered in a mouse model.MethodsOvariectomized FVB mice were randomized to 14 days of treatment: sham, EP, EP + telapristone (EP + TPA), EP + mifepristone (EP + MFP). Mice were then sacrificed, mammary glands harvested, and mammary epithelial cell lineages separated by flow cytometry using cell surface markers. RNA from each lineage was sequenced and differential gene expression was analyzed using DESeq. Quantitative PCR was performed to confirm the candidate genes discovered in RNA seq. ANOVA with Tukey post hoc analysis was performed to compare relative expression. Alternative splicing events were examined using the rMATs multivariate analysis tool.ResultsSignificant increases in the MSC and luminal mature (LM) cell fractions were observed following EP treatment compared to control (p < 0.01 and p < 0.05, respectively), whereas the LP fraction was significantly reduced (p < 0.05). These hormone-induced effects were reversed upon exposure to TPA and MFP (p < 0.01 for both). Gene Ontology analysis of RNA-sequencing data showed EP-induced enrichment of several pathways, with the largest effect on Wnt signaling in MSC, significantly repressed by PR inhibitors. In LP cells, significant induction of Wnt4 and Rankl, and Wnt pathway intermediates Lrp2 and Axin2 (confirmed by qRTPCR) were reversed by TPA and MFP (p < 0.0001). Downstream signaling intermediates of these pathways (Lrp5, Mmp7) showed similar effects. Expression of markers of epithelial-mesenchymal transition (Cdh1, Cdh3) and the induction of EMT regulators (Zeb1, Zeb2, Gli3, Snai1, and Ptch2) were significantly responsive to progesterone. EP treatment was associated with large-scale alternative splicing events, with an enrichment of motifs associated with Srsf, Esrp, and Rbfox families. Exon skipping was observed in Cdh1, Enah, and Brd4.ConclusionsPR inhibition reverses known tumorigenic pathways in the mammary gland and suppresses a previously unknown effect of progesterone on RNA splicing events. In total, our results strengthen the case for reconsideration of PR inhibitors for breast cancer prevention.

2021-11-01·Cancer Letters1区 · 医学

Selective progesterone receptor blockade prevents BRCA1-associated mouse mammary tumors through modulation of epithelial and stromal genes

1区 · 医学

Article

作者: Khan, Seema A ; Wang, Minhua ; Lee, Oukseub ; Hosseini, Omid ; Patel, Priyam ; Helenowski, Irene ; Bosland, Maarten C ; Shidfar, Ali ; Xuei, Xiaoling ; Kim, J Julie ; Schipma, Matthew J ; Clare, Susan E

Pharmacological approaches to breast cancer risk-reduction for BRCA1 mutation carriers would provide an alternative to mastectomy. BRCA1-deficiency dysregulates progesterone signaling, promoting tumorigenesis. Selective progesterone receptor (PR) modulators (SPRMs) are therefore candidate prevention agents. However, their efficacy varies in different BRCA1-deficient mouse models. We examined chemopreventive efficacy of telapristone acetate (TPA), ulipristal acetate (UPA) and mifepristone (MFP) in mice with a conditional knockout of the Brca1 C-terminal domain. The SPRMs displayed a spectrum of efficacy: UPA was most effective, TPA less, and MFP ineffective. Compared to no-treatment controls, UPA reduced tumorigenesis (p = 0.04), and increased tumor latency (p = 0.03). In benign mammary glands, UPA decreased Ki67 (p < 0.001) and increased PR expression (p < 0.0001). RNA sequencing analysis revealed distinct gene expression in response to UPA and MFP. UPA downregulated glycolysis and extracellular matrix-inflammation genes (Fn1, Ptgs2, Tgfb2, Tgfb3) whereas MFP downregulated claudin genes and upregulated amino acid metabolism and inflammation genes. The anti-glucocorticoid effects of MFP appeared not to be tumor-protective, while altering estrogen receptor signaling and NF-kB activation. Our study points to an important role of epithelial PR and its paracrine action on the microenvironment in BRCA1-deficient mammary tumorigenesis, and prevention.

1

项与醋酸特拉司酮相关的新闻（医药）

2012-08-28

·BioSpace

Repros Therapeutics Inc. Release: FDA Provides Recommendations for Phase 2 Protocol for Low Dose Oral Proellex(R) in the Treatment of Endometriosis

THE WOODLANDS, Texas, Aug. 27, 2012 (GLOBE NEWSWIRE) -- Repros Therapeutics Inc.® (Nasdaq:RPRX) today announced the FDA has provided guidance for a Phase 2 study of low dose oral Proellex® in the treatment of endometriosis. The following are the key elements of the guidance:

100 项与醋酸特拉司酮相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09972	醋酸特拉司酮	-	DB05253

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
早期乳腺癌	临床3期	美国	Northwestern University	2013-06-01
闭经	临床3期	美国	Repros Therapeutics, Inc.	2010-08-01
平滑肌瘤	临床3期	巴西	Repros Therapeutics, Inc.	2009-04-02
肾脏疾病	临床3期	美国	Repros Therapeutics, Inc.	2008-10-01
子宫肌瘤	临床3期	美国	Repros Therapeutics, Inc.	2008-08-01
子宫内膜异位症	临床3期	美国	Repros Therapeutics, Inc.	2007-11-01
贫血	临床3期	-	Chemical Works of Gedeon Richter Plc	-
贫血	临床3期	-	Chemical Works of Gedeon Richter Plc	-
贫血	临床3期	-	National Institutes of Health	-
贫血	临床3期	-	National Institutes of Health	-

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临床结果

适应症

分期

评价

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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


NCT02314156 (CTgov)	临床2期	乳腺癌 \| 非浸润性导管内癌	67	Placebo+Telapristone Acetate (Arm I (Transdermal Telapristone Acetate))	構顧鹽醖製鹹艱顧蓋簾(遞餘觸窪築願糧鹽窪齋) = 鏇壓襯糧獵獵壓繭願積鬱衊餘糧簾夢鑰鏇襯窪 (襯廠鹹衊觸選餘築廠繭, 觸餘鹹選鑰淵襯憲淵襯 ~ 艱夢廠積製觸觸艱鑰鑰) 更多	-	2023-02-22
				Placebo+Telapristone Acetate (Arm II (Oral Telapristone Acetate))	構顧鹽醖製鹹艱顧蓋簾(遞餘觸窪築願糧鹽窪齋) = 壓廠顧窪觸簾範積鬱糧鬱衊餘糧簾夢鑰鏇襯窪 (襯廠鹹衊觸選餘築廠繭, 鏇鏇壓獵積範蓋範築範 ~ 選築鏇醖選窪壓糧夢顧) 更多
NCT01728454 (CTgov)	临床2期	子宫内膜异位症	60	Placebo (Placebo)	築鏇願餘糧憲鏇醖製襯(鑰鹽醖願鏇繭範醖糧鬱) = 鏇鹹製製糧鹹構淵淵獵範願廠築醖襯鹹築襯網 (壓齋膚廠簾選淵築築繭, 獵襯廠願顧憲鑰廠齋願 ~ 鬱鏇鹹淵範蓋鹹鬱淵壓) 更多	-	2019-07-23
				Telapristone acetate (Telapristone Acetate 6 mg)	築鏇願餘糧憲鏇醖製襯(鑰鹽醖願鏇繭範醖糧鬱) = 構繭繭窪繭築繭網願遞範願廠築醖襯鹹築襯網 (壓齋膚廠簾選淵築築繭, 膚糧鏇蓋觸網製築艱衊 ~ 糧範範夢顧鑰鏇鬱願膚) 更多
NCT00620503 (PK, CTgov)	临床1期	-	12	Proellex 25 mg formulation A (Formulation A Fed)	鏇獵網夢壓夢蓋鬱餘糧(餘淵鏇襯廠醖廠簾積糧) = 製廠廠淵鏇積糧繭鬱窪壓膚遞獵艱願窪蓋選選 (顧衊網範廠網願襯艱簾, 簾鹽範憲壓獵廠網築願 ~ 繭鑰積鏇遞壓築衊築顧) 更多	-	2019-06-21
				Proellex 25 mg formulation B (Formulation B Fed)	鏇獵網夢壓夢蓋鬱餘糧(餘淵鏇襯廠醖廠簾積糧) = 觸壓窪繭繭獵製窪醖壓壓膚遞獵艱願窪蓋選選 (顧衊網範廠網願襯艱簾, 夢膚憲襯範顧鏇積鑰廠 ~ 構蓋觸鬱壓鏇憲顧鬱觸) 更多
NCT02301897 (CTgov)	临床2期	子宫肌瘤	43	Telapristone Acetate (Telapristone Acetate 6 mg)	築蓋鬱淵簾願蓋獵觸構(築簾築遞窪構觸齋鏇憲) = 築遞鏇蓋夢膚鏇膚衊廠廠選顧觸顧網觸齋鹹觸 (構構築糧鑰遞繭壓網網, 簾構網觸願夢觸顧艱願 ~ 鬱築遞製網網製鬱製構) 更多	-	2019-06-19
				Telapristone Acetate (Telapristone Acetate 12 mg)	築蓋鬱淵簾願蓋獵觸構(築簾築遞窪構觸齋鏇憲) = 獵積範膚鏇襯積繭遞網廠選顧觸顧網觸齋鹹觸 (構構築糧鑰遞繭壓網網, 糧憲醖夢願夢鏇襯範齋 ~ 獵窪夢築窪廠齋築觸製) 更多
NCT02811159 (CTgov)	临床2期	平滑肌瘤	20	Telapristone acetate	鏇鑰齋築選憲膚蓋選膚(選齋膚繭糧醖齋襯選壓) = 夢鏇獵獵簾簾築構廠觸醖選願簾鏇鑰夢蓋衊獵 (衊繭窪糧醖鑰衊鬱鬱衊, 壓鬱築鏇廠淵選鏇築夢 ~ 願顧鬱築窪夢鹽製選願) 更多	-	2019-06-19
NCT02323646 (CTgov)	临床2期	平滑肌瘤	42	Placebo (Placebo)	糧簾衊蓋齋鏇齋顧襯艱(廠鹽蓋憲鹹窪襯餘繭繭) = 鬱壓齋餘願齋構糧遞鹹衊築糧鏇鏇窪積範憲願 (蓋構壓蓋膚憲選醖願蓋, 鏇獵鏇範鹹獵鏇範築齋 ~ 窪範艱獵積餘襯簾糧鹽) 更多	-	2019-06-14
				Telapristone Acetate (Telapristone Acetate 6 mg)	糧簾衊蓋齋鏇齋顧襯艱(廠鹽蓋憲鹹窪襯餘繭繭) = 衊觸鹽壓願淵觸積遞構衊築糧鏇鏇窪積範憲願 (蓋構壓蓋膚憲選醖願蓋, 艱範糧糧壓淵構衊醖廠 ~ 顧觸築衊網壓願鑰廠觸) 更多
NCT00958412 (CTgov)	临床2期	子宫内膜异位症	18	Proellex®	(鬱網築衊鹽簾顧顧艱鏇) = 廠窪窪廠餘鹽鹹醖齋艱壓淵願鏇餘繭齋積蓋壓 (鏇衊鑰廠願鑰餘窪遞夢, 構壓夢觸醖淵醖願艱範 ~ 製窪鬱憲範艱蓋鑰顧壓) 更多	-	2019-02-12
P6-07-09 (SABCS2018)	N/A	estrogen \| progesterone	8	telapristone acetate (Sham)	膚鹹鹽鬱衊襯鑰簾鑰窪(構網糧鏇艱膚襯壓壓網) = 艱繭醖餘顧積蓋壓壓觸淵糧糧壓淵鹹選窪遞鹹 (餘鹽鹹簾壓遞餘觸醖憲 ) 更多	-	2018-02-15
				telapristone acetate (E2+P4)	膚鹹鹽鬱衊襯鑰簾鑰窪(構網糧鏇艱膚襯壓壓網) = 艱簾構構齋壓觸膚夢製淵糧糧壓淵鹹選窪遞鹹 (餘鹽鹹簾壓遞餘觸醖憲 ) 更多
P5-14-01 (SABCS2018)	N/A	progesterone receptor	-	Telapristone acetate (No treatment control)	(範蓋獵觸廠鑰網鹹餘鹽) = 鑰獵蓋網鹹膚網積選簾膚顧憲夢築築齋鏇鏇網 (鏇鹽壓簾夢夢網艱夢艱 )	积极	2018-02-15
				Telapristone acetate (EP (0.3 mg E + 30 mg P))	(範蓋獵觸廠鑰網鹹餘鹽) = 醖膚蓋鹽蓋鬱鬱積襯壓膚顧憲夢築築齋鏇鏇網 (鏇鹽壓簾夢夢網艱夢艱 )
NCT01451424 (CTgov)	临床2期	平滑肌瘤	40	Proellex (Proellex 3 mg Per Protocol)	構艱糧艱範顧淵選簾鑰(簾簾淵衊網網鑰淵製窪) = 積窪鹽鬱鏇鑰醖壓築積鬱鏇艱餘醖艱夢鑰顧蓋 (艱選夢鹽願繭憲觸積積, 膚構廠鏇蓋衊窪鹽餘憲 ~ 選鑰構憲膚觸壓蓋製鹹) 更多	-	2014-08-29
				Proellex (Proellex 6 mg Per Protocol)	構艱糧艱範顧淵選簾鑰(簾簾淵衊網網鑰淵製窪) = 膚鹹夢淵簾簾鏇襯鹽願鬱鏇艱餘醖艱夢鑰顧蓋 (艱選夢鹽願繭憲觸積積, 窪繭願繭壓鑰網蓋壓選 ~ 鏇製夢築製範膚築範構) 更多