Delving into the Latest Updates on Cyproterone Acetate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

CyPat, Cyproterone 17-O-acetate, Cyproterone acetate (JAN/USAN)

+ [6]

Target

AR

Action

antagonists

Mechanism

AR antagonists(Androgen Receptor antagonists)

Therapeutic Areas

NeoplasmsEndocrinology and Metabolic DiseaseSkin and Musculoskeletal Diseases+ [1]

Active Indication

Acne VulgarisHirsutismProstatic Cancer+ [1]

Inactive Indication

Hot Flashes

Originator Organization

Bayer AG

Active Organization

Schering Espana SaBayer Australia Ltd.

Inactive Organization

Barr Laboratories, Inc.

Drug Highest PhaseApproved

First Approval Date

China (25 Oct 2001),

Acne VulgarisHirsutismProstatic Cancer+ [1]

RegulationOrphan Drug (United States)

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Structure/Sequence

Molecular FormulaC24H29ClO4

InChIKeyUWFYSQMTEOIJJG-FDTZYFLXSA-N

CAS Registry427-51-0

OBJECTIVESPharmacovigilance data analysis can accelerate the identification of drug-related safety signals or reassure on the safety profile. This study evaluates the venous thromboembolism (VTE) risk of newer combined oral contraceptive (COC) formulations with natural estrogens, such as estradiol (E2) and estetrol (E4), using data from the EudraVigilance database.STUDY DESIGNWe conducted a disproportionality reporting rate analysis of VTE events associated with various COC formulations by extracting individual case reports from EudraVigilance database up to July 28, 2024. The study compared the proportionality reporting rate between natural estrogen-based COCs (E2 and E4) and conventional synthetic estrogen-based COCs (ethinylestradiol [EE]), with a comparison to EE-levonorgestrel.RESULTSThe analysis revealed that COCs containing natural estrogens exhibited significantly lower proportionality reporting rates for thrombotic events compared to EE-based COCs. Specifically, E4-drospirenone (E4-DRSP) showed the lowest proportionality reporting rate (0.12), similar to progestin-only pills. EE-DRSP had the highest proportionality reporting rate (2.25), suggesting an increased thrombotic risk.CONCLUSIONSThe study supports the safer thrombotic profile of natural estrogen-based COCs, particularly E2 and E4 formulations, over synthetic estrogen-based COCs containing EE. These findings support the hypothesis that E2- and E4-based pills are safer than EE-based pills, aligning with a shift toward safer contraceptive options in clinical practice.IMPLICATIONSNatural estrogens such as E2 and E4 may emerge as safer alternatives to synthetic estrogens like EE, particularly when combined with progestins like DRSP. This multilevel evidence underscores the importance of evidence-based prescribing practices to enhance patient safety and minimize thrombotic risks associated with COC use.

01 Jan 2025·Journal of Ethnopharmacology

Novel detoxifier of spironolactone against triptolide-induced hepatotoxicity through inhibition of RPB1 degradation

Article

ETHNOPHARMACOLOGICAL RELEVANCETriptolide is a major bioactive and toxic ingredient isolated from the traditional Chinese herb Tripterygium wilfordii (T. wilfordii) Hook F. It exhibits potent antitumor, immunosuppressive, and anti-inflammatory biological activities; however, its clinical application is hindered by severe systemic toxicity. Two preparations of T. wilfordii, including T. wilfordii glycoside tablets and T. wilfordii tablets, containing triptolide, are commonly used in clinical practice. However, their adverse side effects, particularly hepatotoxicity, limit their safe use. Therefore, it is crucial to discover potent and specific detoxification medicines for triptolide.AIM OF THE STUDYThis study aimed to investigate the detoxification effects and potential mechanism of action of spironolactone on triptolide-induced hepatotoxicity to provide a potential detoxifying strategy for triptolide, thereby promoting the safe applications of T. wilfordii preparations in clinical settings.MATERIALS AND METHODSCell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and crystal violet staining. Nuclear fragmentation was visualized using 4',6-diamidino-2-phenylindole (DAPI) staining, and protein expression was analyzed by Western blotting. The inhibitory effect of spironolactone on triptolide-induced hepatotoxicity was evaluated by examining the effects of spironolactone on serum alanine aminotransferase and aspartate aminotransferase levels, as well as liver pathology in a mouse model of triptolide-induced acute hepatotoxicity. Furthermore, a survival assay was performed to investigate the effects of spironolactone on the survival rate of mice exposed to a lethal dose of triptolide. The effect of spironolactone on triptolide-induced global transcriptional repression was assessed through 5-ethynyl uridine staining.RESULTSTriptolide treatment decreased the cell viability, increased the nuclear fragmentation and the cleaved caspase-3 levels in both hepatoma cells and hepatocytes. It also increased the alanine aminotransferase and aspartate aminotransferase levels, induced the hepatocyte swelling and necrosis, and led to seven deaths out of 11 mice. The above effects could be mitigated by pretreatment with spironolactone. Additionally, molecular mechanism exploration unveiled that spironolactone inhibited triptolide-induced DNA-directed RNA polymerase II subunit RPB1 degradation, consequently increased the fluorescence intensity of 5-ethynyl uridine staining for nascent RNA.CONCLUSIONSThis study shows that spironolactone exhibits a potent detoxification role against triptolide hepatotoxicity, through inhibition of RPB1 degradation induced by triptolide and, in turn, retardation of global transcriptional inhibition in affected cells. These findings suggest a potential detoxification strategy for triptolide that may contribute to the safe use of T. wilfordii preparations.

01 Jan 2025·Mutation Research - Genetic Toxicology and Environmental Mutagenesis

The transgenic MutaMouse hepatocyte mutation assay in vitro: Mutagenicity and mutation spectra of six substances with different mutagenic mechanisms

Article

Author: Rülker, Claudia ; Tokovenko, Bogdan ; Honarvar, Naveed ; Göpfert, Alina ; Funk-Weyer, Dorothee ; Dammann, Martina ; Schuster, David M ; Landsiedel, Robert ; Eichenlaub, Michael

Mutagenicity testing is a component of the hazard assessment of industrial chemicals, biocides, and pesticides. Mutations induced by test substances can be detected by in vitro and in vivo methods that have been adopted as OECD Test Guidelines. One of these in vivo methods is the Transgenic Rodent Assay (TGRA), OECD test guideline no. 488. An analogous in vitro TGRA has been described, but experience with this test method is limited. In this study, six in vivo TGRA positive mutagens were tested in the in vitro TGRA based on primary MutaMouse hepatocytes. In addition to the functional read-out of the lacZ reporter gene, induced mutations were analysed by next-generation sequencing (NGS). Five of the six in vivo TGRA positive mutagens (N-ethyl-N-nitrosourea (ENU), ethyl methanesulfonate (EMS), mitomycin C (MMC), benzo[a]pyrene (B[a]P), and azathioprine (AZA), but not cyproterone acetate) mutated the lacZ gene in vitro. NGS identified mutations which matched the mutagenic mechanisms described in the literature. The alkylating agent ENU induced a greater proportion of A:T to T:A transversions than did the other alkylating agent, EMS, whereas EMS increased smaller deletions (1-4 bp). G:C to T:A transversions accounted for the majority of mutations identified after treatments with MMC and B[a]P, both of which form monoadducts at the guanine N2 position. AZA induced mainly G:C to A:T transitions, explained by the structural similarity of one of its metabolites to guanine. An increased proportion of mid-size changes (0.3-2.5 kb) was detected only for the crosslinking mutagen MMC. The in vitro TGRA based on primary MutaMouse hepatocytes is a promising in vitro assay for the assessment of mutation induction, reflecting many aspects of the corresponding in vivo TGRA and allowing for mutation spectra analysis to evaluate the induced mutations.

1

News (Medical) associated with Cyproterone Acetate

16 Jul 2019

·www.bioportfolio.com

Canada: National Pharmacare Or ‘Fill The Gaps’?

A national pharmacare program in Canada could make it harder to access higher cost drugs. Related Stories ‘UK Waiver’ For SPCs Proposed In Case Of No-Deal Brexit EMA Reviews Meningioma Risk With Cyproterone Medicines NICE Overcomes UK Reimbursement Doubts Over Forxiga, US FDA Says No To Approval

100 Deals associated with Cyproterone Acetate

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External Link

KEGG	Wiki	ATC	Drug Bank
D01368	Cyproterone Acetate	G03HA01	DB04839

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Acne Vulgaris	China	Schering Espana Sa	25 Oct 2001
Hirsutism	China	Schering Espana Sa	25 Oct 2001
Prostatic Cancer	China	Schering Espana Sa	25 Oct 2001
Puberty, Precocious	China	Schering Espana Sa	25 Oct 2001

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hot Flashes	Preclinical	United States	Barr Laboratories, Inc.	01 Dec 1999
Prostatic Cancer	Preclinical	United States	Barr Laboratories, Inc.	01 Dec 1999

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ENDO2024	Not Applicable	-	-	Cyproterone Acetate 12.5mg	ayqvpnrmkf(vhhxslxkak) = rrsssupeft ygcuxugjrs (mdksonloel, 158.6) View more	-	01 Jun 2024
				Spironolactone 100mg	ayqvpnrmkf(vhhxslxkak) = vhlnbciofi ygcuxugjrs (mdksonloel, 112.03) View more
SAT397 (ENDO2023)	Not Applicable	-	89	Cyproterone Acetate 12.5 mg/day	fchpwnxddc(ggtyhmdbnm) = wfzfgxvqde ddzgtpotic (axugttrocn, ( - 25.86) to ( to 1.58)) View more	Positive	05 Oct 2023
				Standard Dose of Cyproterone Acetate	fhhcoitjhk(mmaeyewoem) = lfhiiqgoxw mreixkrzyu (tfuqucxyeb )
ESH2023	Not Applicable	-	56	Cyproterone acetate <25 mg/day	yjpwgpimlw(dwqxmpepkq) = zlzlzbisjn xqqplnxney (grshojlvjg ) View more	Negative	01 Jun 2023
				Cyproterone acetateoestradiol (Reference population (oestradiol without antiandrogen))	yjpwgpimlw(dwqxmpepkq) = jdgakbbbdt xqqplnxney (grshojlvjg ) View more
SUN-042 (ENDO2020)	Not Applicable	-	-	Low Dose Cyproterone Acetate	ypkxakycjq(gxxpckfker) = four cases in the High Dose Cyproterone Acetate group aonyuknlgr (twhtvbmiay ) View more	Positive	08 May 2020
				High Dose Cyproterone Acetate
ESPE2016	Not Applicable	-	27	Cyproterone Acetate (CA)	(hykfnesvlb) = became more unfavourable during CA, but restored with addition of E quxnxkbdjt (qvzxccswzt ) View more	-	10 Sep 2016
				Cyproterone Acetate + Estrogens (CA+E)
ESPE2014	Not Applicable	Fibrous Dysplasia, Polyostotic \| Puberty, Precocious	-	Ketoconazole	gjnijcddzc(xsdpghyzmk) = jcwanposik llqmeukgmt (djwacjecep )	-	18 Sep 2014
				Cyproterone Acetate	gjnijcddzc(xsdpghyzmk) = svndvimwpn llqmeukgmt (djwacjecep )