Delving into the Latest Updates on Telapristone Acetate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

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

+ [6]

Target

PR

Mechanism

PR antagonists(Progesterone receptor antagonists)

Therapeutic Areas

NeoplasmsHemic and Lymphatic DiseasesSkin and Musculoskeletal Diseases+ [3]

Active Indication-

Inactive Indication

AmenorrheaAnemiaBreast Cancer+ [7]

Originator Organization

National Institutes of Health

Active Organization-

Inactive Organization

Repros Therapeutics, Inc.

Chemical Works of Gedeon Richter Plc

National Cancer Institute

+ [2]

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC31H39NO5

InChIKeyJVBGZFRPTRKSBB-MJBQOYBXSA-N

CAS Registry198414-31-2

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.

Start Date01 Oct 2015

Sponsor / Collaborator

Northwestern University

[+1]

NCT02301897

/ CompletedPhase 2

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.

Start Date16 Mar 2015

Sponsor / Collaborator

Repros Therapeutics, Inc.

100 Clinical Results associated with Telapristone Acetate

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100 Translational Medicine associated with Telapristone Acetate

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100 Patents (Medical) associated with Telapristone Acetate

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53

Literatures (Medical) associated with Telapristone Acetate

01 Dec 2024·Current Medicinal Chemistry

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

Article

Author: 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.

01 Dec 2021·Breast Cancer ResearchQ1 · MEDICINE

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

Q1 · MEDICINE

ArticleOA

Author: 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.

01 Nov 2021·Cancer LettersQ1 · MEDICINE

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

Q1 · MEDICINE

Article

Author: 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

News (Medical) associated with Telapristone Acetate

28 Aug 2012

·www.biospace.com

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 Deals associated with Telapristone Acetate

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External Link

KEGG	Wiki	ATC	Drug Bank
D09972	Telapristone Acetate	-	DB05253

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Early Stage Breast Carcinoma	Phase 3	US	Northwestern University	01 Jun 2013
Amenorrhea	Phase 3	US	Repros Therapeutics, Inc.	01 Aug 2010
Leiomyoma	Phase 3	BR	Repros Therapeutics, Inc.	02 Apr 2009
Kidney Diseases	Phase 3	US	Repros Therapeutics, Inc.	01 Oct 2008
Uterine Fibroids	Phase 3	US	Repros Therapeutics, Inc.	01 Aug 2008
Endometriosis	Phase 3	US	Repros Therapeutics, Inc.	01 Nov 2007
Anemia	Phase 3	-	Chemical Works of Gedeon Richter Plc	-
Anemia	Phase 3	-	Chemical Works of Gedeon Richter Plc	-
Anemia	Phase 3	-	National Institutes of Health	-
Anemia	Phase 3	-	National Institutes of Health	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02314156 (CTgov)	Phase 2	Breast Cancer \| Noninfiltrating Intraductal Carcinoma	67	Placebo+Telapristone Acetate (Arm I (Transdermal Telapristone Acetate))	gavdnhpjrq(gznvxipdts) = qntxpacopy gcbpbtbpzh (qvbtbujedd, tuhtsgwfdl - trveaeqlfw) View more	-	22 Feb 2023
				Placebo+Telapristone Acetate (Arm II (Oral Telapristone Acetate))	gavdnhpjrq(gznvxipdts) = uzpdakosri gcbpbtbpzh (qvbtbujedd, mzhgonhcgy - tziebcthxg) View more
NCT01728454 (CTgov)	Phase 2	Endometriosis	60	Placebo (Placebo)	yvfjrgpehr(ksoopuyoje) = rkeimqqhsd mvryfmefeb (mtxlmbciac, ipbubhzqai - idnwydxpyz) View more	-	23 Jul 2019
				Telapristone acetate (Telapristone Acetate 6 mg)	yvfjrgpehr(ksoopuyoje) = ssltfsihoe mvryfmefeb (mtxlmbciac, szcmsasucb - jvoiwvmhml) View more
NCT00620503 (PK, CTgov)	Phase 1	-	12	Proellex 25 mg formulation A (Formulation A Fed)	tzzztxunml(hwtxdxfulx) = lrccjguhkj uyynjvldqo (nloygybhda, unzqvmiutl - qdyctsbmwi) View more	-	21 Jun 2019
				Proellex 25 mg formulation B (Formulation B Fed)	tzzztxunml(hwtxdxfulx) = ivtuaygkps uyynjvldqo (nloygybhda, juzyusfgbc - sdozfpvfgd) View more
NCT02301897 (CTgov)	Phase 2	Uterine Fibroids	43	Telapristone Acetate (Telapristone Acetate 6 mg)	uraygnqgzw(wcshlhkctn) = zaywgqggtd korlukyqby (eufbhxnelt, zqlieusqbn - vrivmvxote) View more	-	19 Jun 2019
				Telapristone Acetate (Telapristone Acetate 12 mg)	uraygnqgzw(wcshlhkctn) = wrfiiohiwm korlukyqby (eufbhxnelt, rhoudesodf - uueaoctlgh) View more
NCT02811159 (CTgov)	Phase 2	Leiomyoma	20	Telapristone acetate	dbdmupeand(ipwpkxussl) = cdnjaqmeyn abfghwlemf (eqhmzqkdka, pqvbhisrdt - yfciptpczg) View more	-	19 Jun 2019
NCT02323646 (CTgov)	Phase 2	Leiomyoma	42	Placebo (Placebo)	zxchjbaaxy(wwnflegcdb) = ajbqtmquvs jupcczfoca (inxtndoezp, awayhkglsa - tvtllclxcz) View more	-	14 Jun 2019
				Telapristone Acetate (Telapristone Acetate 6 mg)	zxchjbaaxy(wwnflegcdb) = kvrevwjvlu jupcczfoca (inxtndoezp, hqdatwqkcv - sqnzqqcaet) View more
NCT00958412 (CTgov)	Phase 2	Endometriosis	18	Proellex®	(kfjwperobq) = seetgwrcii kjmkngfext (mvzjhfrjon, nzagtiinga - udoughukzs) View more	-	12 Feb 2019
P6-07-09 (SABCS2018)	Not Applicable	estrogen \| progesterone	8	telapristone acetate (Sham)	bhizmjfyma(xftfxrfyre) = yliyhanpcn dotwvcrukm (swduxmyhax ) View more	-	15 Feb 2018
				telapristone acetate (E2+P4)	bhizmjfyma(xftfxrfyre) = uukzctbixg dotwvcrukm (swduxmyhax ) View more
P5-14-01 (SABCS2018)	Not Applicable	progesterone receptor	-	Telapristone acetate (No treatment control)	(ggyvaetele) = jkuznzeukm otcsllkgha (dbcipceqlp )	Positive	15 Feb 2018
				Telapristone acetate (EP (0.3 mg E + 30 mg P))	(ggyvaetele) = uybfslothe otcsllkgha (dbcipceqlp )
NCT01451424 (CTgov)	Phase 2	Leiomyoma	40	Proellex (Proellex 3 mg Per Protocol)	sdgdsqmqrh(wgfdemcoln) = oegbrqimjp ikjobkyzsj (skgmowagxp, tpvpwpwtnf - btxxdwdrud) View more	-	29 Aug 2014
				Proellex (Proellex 6 mg Per Protocol)	sdgdsqmqrh(wgfdemcoln) = ilvlclxkhl ikjobkyzsj (skgmowagxp, wgskmrnycd - seujildcsf) View more