Cyproterone Acetate

Cyproterone Acetate (CPA) is a steroidal progestogen and potent antiandrogen. It is used in oral contraceptives, as a component of hormone therapy, and in the treatment of certain medical conditions, particularly androgen-related issues.

Tags
cyproterone acetate
MOL SDF CML

Identifiers

Abbreviation

CPA

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References

Names

6-chloro-3,20-dioxo-1β,2β-dihydro-3'H-cyclopropa[1,2]pregna-1,4,6-trien-17-yl acetate

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References

  1. BP 2017: Cyproterone Acetate monograph.
    2. (View all citations for this reference)

CASRN

427-51-0

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References

PubChem CID

9880

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References

  1. PubChem: Cyproterone Acetate (View all citations for this reference)

ECHA InfoCard

  • 100.006.409
  • EC / List #: 207-048-3

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References

  1. ECHA: Cyproterone Acetate (View all citations for this reference)

IUPHAR/BPS

2865

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References

  1. IUPHAR: Cyproterone Acetate (View all citations for this reference)

DrugBank Accession Number

DB04839

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References

  1. DrugBank: Cyproterone Acetate
    Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2017 Nov 8. doi: 10.1093/nar/gkx1037     (View all citations for this reference)

UNII

4KM2BN5JHF

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References

  1. UNII: Cyproterone Acetate (View all citations for this reference)

KEGG Entry Number

D01368

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References

  1. KEGG: Cyproterone Acetate (View all citations for this reference)

ChEBI ID

CHEBI:50743

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References

  1. ChEBI: Cyproterone Acetate (View all citations for this reference)

ChEMBL ID

CHEMBL139835

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References

  1. ChEMBL: Cyproterone Acetate (View all citations for this reference)

ChemSpider ID

9496

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References

  1. ChemSpider: Cyproterone Acetate (View all citations for this reference)

PDB

CA4

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References

  1. PDB: Cyproterone Acetate (View all citations for this reference)

ATC Code(s)

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References

  1. DrugBank: Cyproterone Acetate
    Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2017 Nov 8. doi: 10.1093/nar/gkx1037     (View all citations for this reference)

Physical & Chemical Properties

Molecular Formula

C24H29ClO4

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References

Molecular Weight

416.9 g/mol

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References

Appearance

White or almost white crystalline powder

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References

  1. BP 2017: Cyproterone Acetate monograph.
    2. (View all citations for this reference)
  2. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)

Melting Point

BP: About 210 °C
DrugBank, IARC, Toxnet: 200-201 °C

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References

  1. BP 2017: Cyproterone Acetate monograph.
    2. (View all citations for this reference)
  2. DrugBank: Cyproterone Acetate
    Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2017 Nov 8. doi: 10.1093/nar/gkx1037     (View all citations for this reference)
  3. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)
  4. Toxnet: Cyproterone Acetate (View all citations for this reference)

Solubility

Practically insoluble in water, very soluble in methylene chloride, freely soluble in acetone, soluble in methanol, sparingly soluble in anhydrous ethanol

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References

  1. BP 2017: Cyproterone Acetate monograph.
    2. (View all citations for this reference)
  2. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)

Specific Optical Rotation

+152 to +157, 0.25 g dried substance in acetone, dilute to 25.0 mL

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References

  1. BP 2017: Cyproterone Acetate monograph.
    2. (View all citations for this reference)
  2. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)

Storage Conditions

Store in a tightly closed container in a dry, ventilated location, recommended at 2-8 °C. Do not store above 25 °C.

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References

  1. Toxnet: Cyproterone Acetate (View all citations for this reference)

Toxicology

GHS Hazard Code(s)

Class Category Code Description
Acute Dermal Toxicity 4 H312 Harmful in contact with skin
Acute Inhalation Toxicity 4 H332 Harmful if inhaled
Carcinogenicity 2 H351 Suspected of causing cancer if inhaled
Reproductive Toxicity 1A H360FD May damage fertility. May damage the unborn child
Specific Target Organ Toxicity, Repeated Exposure 2 H373 Causes damage to organs through prolonged or repeated exposure

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References

  1. ECHA: Cyproterone Acetate (View all citations for this reference)

Mutagenicity

Not found to be mutagenic in the Ames Salmonella/microsome direct plate incorporation protocol.

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References

  1. Lang, R.; Reimann, R. Studies for a Genotoxic Potential of Some Endogenous and Exogenous Sex Steroids. I. Communication: Examination for the Induction of Gene Mutations Using the Ames Salmonella/microsome Test and the HGPRT Test in V79 Cells. Environ. Mol. Mutagen. 1993, 21 (3), 272–304. (View all citations for this reference)

Genotoxicity

Reports vary. Siddique et al. found CPA to be genotoxic to human lymphocytes at 20 and 30 μm using chromosomal aberrations, mitotic index, and sister chromatid exchanges. Reimann et al. did not find CPA to be genotoxic in human lymphocyte assay in vitro and mouse bone marrow micronucleus test in vivo.

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References

  1. Toxnet: Cyproterone Acetate (View all citations for this reference)
  2. Siddique, Y. H.; Afzal, M. Genotoxic Potential of Cyproterone Acetate: A Possible Role of Reactive Oxygen Species. Toxicol. Vitr. 2005, 19 (1), 63–68. (View all citations for this reference)
  3. (1) Reimann, R.; Kalweit, S.; Lang, R. Studies for a Genotoxic Potential of Some Endogenous and Exogenous Sex Steroids. II. Communication: Examination for the Induction of Cytogenetic Damage Using the Chromosomal Aberration Assay on Human Lymphocytes in Vitro and the Mouse Bone Marrow Micronucleus Test in vivo. Environ. Mol. Mutagen. 1996, 28 (2), 133–144. (View all citations for this reference)

LD50

rat intraperitoneal: 565 mg/kg
mouse intraperitoneal: 3300 mg/kg

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References

  1. Toxnet: Cyproterone Acetate (View all citations for this reference)

TD50

mouse: 21.9 mg/kg/day

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References

  1. The Carcinogenic Potency Database. (View all citations for this reference)

Biochemistry & Pharmacology

Progesterone Receptor Activity

Agonist

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References

  1. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)

Androgen Receptor Activity

Potent antagonist

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References

  1. Stanczyk, F. Z.; Archer, D. F.; Bhavnani, B. R., Ethinyl estradiol and 17 beta-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment. Contraception 2013, 87 (6), 706-727.
    2. (View all citations for this reference)
  2. Ruan, X.; Seeger, H.; Mueck, A. O., The pharmacology of nomegestrol acetate. Maturitas 2012, 71 (4), 345-53.
    3. (View all citations for this reference)
  3. Lello, S., Nomegestrol Acetate Pharmacology, Safety Profile and Therapeutic Efficacy. Drugs 2010, 70 (5), 541-559.
    4. (View all citations for this reference)
  4. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)
  5. KEGG: Cyproterone Acetate (View all citations for this reference)
  6. Krattenmacher, R. Drospirenone: Pharmacology and Pharmacokinetics of a Unique Progestogen. Contraception 2000, 62 (1), 29–38. (View all citations for this reference)

Estrogen Receptor Activity

Antagonist

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References

  1. Ruan, X.; Seeger, H.; Mueck, A. O., The pharmacology of nomegestrol acetate. Maturitas 2012, 71 (4), 345-53.
    2. (View all citations for this reference)
  2. Lello, S., Nomegestrol Acetate Pharmacology, Safety Profile and Therapeutic Efficacy. Drugs 2010, 70 (5), 541-559.
    3. (View all citations for this reference)
  3. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)

Glucocorticoid Receptor Activity

Agonist

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References

  1. Hapgood, J. P.; Africander, D.; Louw, R.; Ray, R. M.; Rohwer, J. M., Potency of progestogens used in hormonal therapy: toward understanding differential actions. J Steroid Biochem Mol Biol 2013, 142, 39-47.
    2. (View all citations for this reference)
  2. Ruan, X.; Seeger, H.; Mueck, A. O., The pharmacology of nomegestrol acetate. Maturitas 2012, 71 (4), 345-53.
    3. (View all citations for this reference)
  3. Lello, S., Nomegestrol Acetate Pharmacology, Safety Profile and Therapeutic Efficacy. Drugs 2010, 70 (5), 541-559.
    4. (View all citations for this reference)
  4. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)

Mineralocorticoid Receptor Activity

No activity

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References

  1. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)
  2. Hapgood, J. P.; Africander, D.; Louw, R.; Ray, R. M.; Rohwer, J. M., Potency of progestogens used in hormonal therapy: toward understanding differential actions. J Steroid Biochem Mol Biol 2013, 142, 39-47.
    3. (View all citations for this reference)
  3. Ruan, X.; Seeger, H.; Mueck, A. O., The pharmacology of nomegestrol acetate. Maturitas 2012, 71 (4), 345-53.
    4. (View all citations for this reference)
  4. Lello, S., Nomegestrol Acetate Pharmacology, Safety Profile and Therapeutic Efficacy. Drugs 2010, 70 (5), 541-559.
    5. (View all citations for this reference)
  5. Krattenmacher, R. Drospirenone: Pharmacology and Pharmacokinetics of a Unique Progestogen. Contraception 2000, 62 (1), 29–38. (View all citations for this reference)

Bioavailability

88%

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References

  1. Toxnet: Cyproterone Acetate (View all citations for this reference)

Elimination Half-Life (t1/2)

Drugbank: 38 h (oral), 96 h (intramuscular)
Toxnet: 43.9 +/- 12.8 h from two 50 mg CPA tablets

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References

  1. DrugBank: Cyproterone Acetate
    Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2017 Nov 8. doi: 10.1093/nar/gkx1037     (View all citations for this reference)
  2. Toxnet: Cyproterone Acetate (View all citations for this reference)

Serum Protein Binding

Almost exclusively bound to albumin. 3.5-4% unbound.

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References

  1. Toxnet: Cyproterone Acetate (View all citations for this reference)

Metabolism

Metabolized by CYP3A4

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References

  1. DrugBank: Cyproterone Acetate
    Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2017 Nov 8. doi: 10.1093/nar/gkx1037     (View all citations for this reference)

Excretion

60% in the bile and 33% through kidneys.

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References

  1. DrugBank: Cyproterone Acetate
    Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2017 Nov 8. doi: 10.1093/nar/gkx1037     (View all citations for this reference)

Cmax

285 ng/mL from two 50 mg CPA tablets

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References

  1. Toxnet: Cyproterone Acetate (View all citations for this reference)

Enzyme Interactions

Inhibits CYP19A1, CYP2D6 (DrugBank). May inhibit CYP2C8 (Toxnet).

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References

  1. DrugBank: Cyproterone Acetate
    Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2017 Nov 8. doi: 10.1093/nar/gkx1037     (View all citations for this reference)

Indications

Advanced prostate carcinoma, metastatic hormone refractory prostate cancer, paraphilia, severe acne.

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References

  1. DrugBank: Cyproterone Acetate
    Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2017 Nov 8. doi: 10.1093/nar/gkx1037     (View all citations for this reference)

Metabolites

Name
Structure
Notes
15β-Hydroxycyproterone Acetate
structure

Formed by CYP3A4.

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Impurities

Name
Structure
CASRN
Other Names & Identifiers
Cyproterone Acetate 1-Chloromethyl Derivative
structure

  • BP Cyproterone Tablets Impurity 2
  • 17α-Hydroxy-6-chloro-1α-chloromethylpregna-4,6-diene-3,20-dione

Cyproterone Acetate Chlorohydrin Derivative
structure

  • BP CPA Impurity G
  • BP Cyproterone Tablets Impurity 1
  • 6β-Chloro-7α,17α-dihydroxy-1α,2α-methylenepregna-4-ene-3,20-dione
  • 6β-Chloro-7α-hydroxy-3,20-dioxo-1β,2β-dihydro-3'H-cyclopropa[1,2]pregna-1,4-dien-17-yl Acetate

6α,7α-Epoxy-3,20-dioxo-1β,2β-dihydro-3′H-cyclopropa[1,2]pregna-1,4-dien-17-yl Acetate
structure

  • BP CPA Impurity J

6-Chloro-3,20-dioxopregna-1,4,6-trien-17-yl Acetate
structure

  • BP CPA Impurity I

3,20-Dioxopregna-1,4-diene-17-yl Acetate
structure

  • BP CPA Impurity H

View All (11)