Cyproterone acetate

• Catalog No.: S2042
• CAS Number: 427-51-0
• M. F.: C24H29ClO4
• M. W.: 416.93766
• Storage: -20°C

SYNONYMS

• IUPAC name: (1S,2S,3S,5R,11R,12S,15R,16S)-15-acetyl-9-chloro-2,16-dimethyl-6-oxopentacyclo[9.7.0.0^{2,8}.0^{3,5}.0^{12,16}]octadeca-7,9-dien-15-yl acetate
• IUPAC Traditional name: cyproterone acetate

DATABASE IDS

• CAS Number: 427-51-0

PROPERTIES

• Target: Estrogen receptor
• Salt Data: acetate
• Storage Condition: -20°C

DETAILS

Description (English)

Biological Activity

• Description: Cyproterone acetate is an androgen receptor (AR) antagonist with IC50 of 7.1 nM.
• Targets: AR
• IC50: 7.1 nM ^[1]
• In Vitro: Cyproterone acetate clearly shows antagonistic properties, while being a partial agonist also, showing agonism for the AR, with EC50 of 4.0 μM, at relatively high concentrations. ^[1] In the presence of 10 nM Testosterone, low concentrations of Cyproterone acetate inhibits T-stimulated transcription of 3XHRE-LUC, but at higher concentrations, transcription is stimulated. ^[2]
• In Vivo: LH levels in Cyproterone acetate-treated rats do not dip below pretreatment levels, although they does not increase as much in the rats treated with 3.2 mg Cyproterone acetate/kg/day as in those which received 0.2 mg Cyproterone acetate/kg/day. ^[2] Cyproterone acetate exhibits direct negative effect on reproductive organs weight and significant reducing effect on sperm count and Ca^2+ contents. SOD and GST activities significantly decrease in addition to significant increase in NO, MDA contents reflecting the oxidative status of testis in Cyproterone acetate treated rats. ^[3] Cyproterone acetate treatment plus artificial long days in autumn has a negative effect on sperm motility and sperm morphology. ^[4] Androgen receptor occupation by Cyproterone acetate preferentially reduces the levels of spermatidal protamine in testis and spermatozoa involved in nuclear chromatin condensation. ^[5]
• Clinical Trials: Cyproterone acetate has entered in a phase III clinical trial in the treatment of anxiety disorder, prostate cancer, sexual dysfunction, urinary complications and long-term effects secondary to cancer therapy in adults.

Combination Therapy

• Description: Cyproterone acetate plus bicalutamide, buserelin, flutamide, goserelin, leuprolide acetate and nilutamide has entered in a phase III clinical trial in the treatment of prostate cancer.

Protocol

• Protocol: Kinase Assay ^[1]
• AR and ERα CALUX bioassays: U2-OS cells are transfected with 3× HRE-TATA-Luc and pSG5-neo-hAR, using calcium phosphate precipitation to generate AR CALUX cells. AR and ERα CALUX cells are plated in 96-well plates (6000 cells/well) with phenol red-free DF medium supplemented with 5% dextran-coated charcoal-stripped FCS (DCC-FCS) at a volume of 200 μL per well. Two days later, the medium is refreshed, and cells are incubated with human or fetal serum (0–10% [v/v]) or Cyproterone acetate (dissolved in ethanol or DMSO) in triplicate at a 1:1000 dilution. In case of serum incubation, final serum concentration is 10% (v/v), and lower percentages of the tested sera are supplemented with DCC-FCS. After 24 hours the medium is removed, cells are lysed in 30 μL Triton-lysis buffer and measured for luciferase activity using a luminometer for 0.1 min/well.
• Protocol: Animal Study ^[2]
• Animal Models: Castrate male SD rat
• Formulation: Ethanol
• Doses: 0.2 mg /kg/day
• Administration: Administered via s.c.

References

• References: [1] Sonneveld E, et al. Toxicol Sci. 2005, 83(1), 136-148.
• References: [2] Attardi BJ, et al. Mol Cell Endocrinol. 2010, 328(1-2), 16-21.
• References: [3] Arafa NM. Pak J Biol Sci. 2010, 13(20), 966-976.
• References: [4] Santiago-Moreno J, et al. J Endocrinol. 2012.
• References: [5] Aleem M, et al. Contraception. 2005, 71(5), 379-391.

REFERENCES

• Sonneveld E, et al. Toxicol Sci. 2005, 83(1), 136-148.
• Attardi BJ, et al. Mol Cell Endocrinol. 2010, 328(1-2), 16-21.
• Arafa NM. Pak J Biol Sci. 2010, 13(20), 966-976.
• Santiago-Moreno J, et al. J Endocrinol. 2012.
• Aleem M, et al. Contraception. 2005, 71(5), 379-391.