(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

• ChemBase ID: 73284
• Molecular Formular: C24H29ClO4
• Molecular Mass: 416.93766
• Monoisotopic Mass: 416.17543709
• SMILES: [C@H]12C(=O)C=C3[C@]([C@H]1C2)([C@@H]1[C@@H](C=C3Cl)[C@H]2[C@](CC1)([C@](CC2)(C(=O)C)OC(=O)C)C)C
• Canonical SMILES: CC(=O)O[C@@]1(CC[C@@H]2[C@]1(C)CC[C@H]1[C@H]2C=C(C2=CC(=O)[C@H]3[C@@H]([C@]12C)C3)Cl)C(=O)C
• InChI: InChI=1S/C24H29ClO4/c1-12(26)24(29-13(2)27)8-6-16-14-10-20(25)19-11-21(28)15-9-18(15)23(19,4)17(14)5-7-22(16,24)3/h10-11,14-18H,5-9H2,1-4H3/t14-,15+,16-,17-,18-,22-,23-,24-/m0/s1
• InChIKey: UWFYSQMTEOIJJG-FDTZYFLXSA-N

NAMES AND DATABASE IDS

Names

• 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; (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,^5.0^1^2,^1^6]octadeca-7,9-dien-15-yl acetate
• IUPAC Traditional name: cyproterone acetate
• Synonyms: Cyproterone acetate; (1β,2β)-17-(Acetyloxy)-6-chloro-1,2-dihydro-3'H-cyclopropa[1,2]pregna-1,4,6-triene-3,20-dione; 1,2α-Methylene-6-chloro-pregna-4,6-diene-3,20-dione 17α-Acetate; 6-Chloro-17-hydroxy-1α,2α-methylenepregna-4,6-diene-3,20-dione Acetate; Androcur; CPA; Cyprostat; Cyproterone 17-O-Acetate; Cyproterone 17α-Acetate; Cyproviron; NSC 81430; SH 714; 6-Chloro-1β,2β-dihydro-17-hydroxy-3′H-cyclopropa(1,2)-pregna-1,4,6-triene-3,20-dione acetate; Cyproterone acetate

Database IDs

• CAS Number: 427-51-0
• EC Number: 207-048-3
• MDL Number: MFCD00864671
• PubChem SID: 162038204; 24278309
• PubChem CID: 9880

CALCULATED PROPERTIES

• Acid pKa: 17.829681
• H Acceptors: 3
• H Donor: 0
• LogD (pH = 5.5): 3.638857
• LogD (pH = 7.4): 3.638857
• Log P: 3.638857
• Molar Refractivity: 111.8095 cm^3
• Polarizability: 43.571102 Å^3
• Polar Surface Area: 60.44 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: Chloroform; Ethyl Acetate
• Apperance: White Solid
• Melting Point: 209-211°C

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• RTECS: GZ2230000
• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 20/21/22-40
• Safety Statements: 22-36
• GHS Pictograms: GHS07; GHS08
• GHS Signal Word: Warning
• GHS Hazard statements: H312-H332-H351
• GHS Precautionary statements: P280
• Personal Protective Equipment: Eyeshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges
• Storage Temperature: 2-8°C

Pharmacology Properties

• Target: Estrogen receptor
• Gene Information: human ... AR(367)mouse ... Nr3c1(14815)rat ... Ar(24208)

Product Information

• Purity: ≥98%
• Salt Data: acetate

DETAILS

Selleck Chemicals - S2042

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.

Sigma Aldrich - C3412

Biochem/physiol Actions
Synthetic steroid; androgen antagonist; potent inhibitor of leukocyte migration through endothethial cell monolayers. Liver tumor promoter in experimental animal model.1 Liver tumor promotion appears to be female gender-specific, as formation of an active metabolite that forms DNA adducts.2
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. C3412.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

Toronto Research Chemicals - C989100

The free alcohol is an anti-androgen; the acetate is both an anti-androgen and a progestogen. Combined with estrogen it is used in the treatment of acne.

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.
• Moltz, L., et al.: Contraception, 21, 393 (1980)
• Hammerstein, J., et al.: J. Steroid Biochem., 29, 591 (1983)