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Identification
NameCyproterone acetate
Accession NumberDB04839
TypeSmall Molecule
GroupsApproved, Investigational
Description

An anti-androgen that, in the form of its acetate (cyproterone acetate), also has progestational properties. It is used in the treatment of hypersexuality in males, as a palliative in prostatic carcinoma, and, in combination with estrogen, for the therapy of severe acne and hirsutism in females. [Pubchem]

Structure
Thumb
Synonyms
SynonymLanguageCode
Cyproterone 17-O-acetateNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AndrocurBayer
CyprostatBayer
Brand mixtures
Brand NameIngredients
Diane-35Cyproterone Acetate + Ethinyl Estradiol
CategoriesNot Available
CAS number427-51-0
WeightAverage: 416.938
Monoisotopic: 416.175437123
Chemical FormulaC24H29ClO4
InChI KeyUWFYSQMTEOIJJG-HEULQOMWNA-N
InChI
InChI=1/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-/s2
IUPAC Name
(1S,2S,3S,5R,11R,12S,15R,16S)-15-acetyl-9-chloro-2,16-dimethyl-6-oxopentacyclo[9.7.0.0²,⁸.0³,⁵.0¹²,¹⁶]octadeca-7,9-dien-15-yl acetate
SMILES
[H][C@@]12C[C@]1([H])[C@@]1(C)C(=CC2=O)C(Cl)=C[C@@]2([H])[C@]3([H])CC[C@](OC(C)=O)(C(C)=O)[C@@]3(C)CC[C@]12[H]
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassGluco/mineralocorticoids, Progestogins and Derivatives
Direct parentGluco/mineralocorticoids, Progestogins and Derivatives
Alternative parentsKetosteroids; Halogenated Steroids; Hydroxysteroids; Tropones; Tertiary Alcohols; Ketones; Cyclic Alcohols and Derivatives; Polyamines; Enolates; Organochlorides
Substituents6-halo-steroid; 3-keto-steroid; 17-hydroxy-steroid; 20-keto-steroid; tropone; cyclic alcohol; tertiary alcohol; ketone; polyamine; enolate; organochloride; organohalogen; alcohol; carbonyl group
Classification descriptionThis compound belongs to the gluco/mineralocorticoids, progestogins and derivatives. These are steroids whose structure is based on an hydroxylated prostane moiety.
Pharmacology
IndicationFor the palliative treatment of patients with advanced prostatic carcinoma.
PharmacodynamicsCyproterone is an antiandrogen. It suppresses the actions of testosterone (and its metabolite dihydrotestosterone) on tissues. It acts by blocking androgen receptors which prevents androgens from binding to them and suppresses luteinizing hormone (which in turn reduces testosterone levels).
Mechanism of actionThe direct antiandrogenic effect of cyproterone is blockage of the binding of dihydrotestosterone to the specific receptors in the prostatic carcinoma cell. In addition, cyproterone exerts a negative feed-back on the hypothalamo-pituitary axis, by inhibiting the secretion of luteinizing hormone resulting in diminished production of testicular testosterone.
AbsorptionCompletely absorbed following oral administration.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Primarily hepatic. Cyproterone acetate is metabolized by the CYP3A4 enzyme, forming the active metabolite 15beta-hydroxycyproterone acetate, which retains its antiandrogen activity, but has reduced progestational activity.

SubstrateEnzymesProduct
Cyproterone acetate
Not Available
15beta-hydroxycyproterone acetateDetails
Route of eliminationIt is excreted approximately 60% in the bile and 33% through the kidneys.
Half lifeElimination Following oral or intramuscular administration, the plasma half-life is 38 and 96 hours, respectively.
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9673
Caco-2 permeable + 0.7033
P-glycoprotein substrate Substrate 0.7292
P-glycoprotein inhibitor I Inhibitor 0.5265
P-glycoprotein inhibitor II Non-inhibitor 0.9016
Renal organic cation transporter Non-inhibitor 0.8036
CYP450 2C9 substrate Non-substrate 0.8
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Substrate 0.7834
CYP450 1A2 substrate Non-inhibitor 0.8944
CYP450 2C9 substrate Non-inhibitor 0.7229
CYP450 2D6 substrate Non-inhibitor 0.8951
CYP450 2C19 substrate Non-inhibitor 0.737
CYP450 3A4 substrate Non-inhibitor 0.8309
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8919
Ames test Non AMES toxic 0.7067
Carcinogenicity Non-carcinogens 0.926
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 1.8261 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9704
hERG inhibition (predictor II) Non-inhibitor 0.6939
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
LiquidIntramuscular
TabletOral
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point200-201Wiechert, R.; U S . Patent 3,234,093; February 8, 1966; assigned to Schering AG, Germany.
Predicted Properties
PropertyValueSource
Water Solubility0.00152ALOGPS
logP3.81ALOGPS
logP3.64ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)17.83ChemAxon
pKa (Strongest Basic)-5.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area60.44 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity111.81 m3·mol-1ChemAxon
Polarizability44.65 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Aranya Manosroi, “Synthesis of cyproterone acetate.” U.S. Patent US20040024230, issued February 05, 2004.

US20040024230
General Reference
  1. Giorgi EP, Shirley IM, Grant JK, Stewart JC: Androgen dynamics in vitro in the human prostate gland. Effect of cyproterone and cyproterone acetate. Biochem J. 1973 Mar;132(3):465-74. Pubmed
  2. Pham-Huu-Trung MT, de Smitter N, Bogyo A, Girard F: Effects of cyproterone acetate on adrenal steroidogenesis in vitro. Horm Res. 1984;20(2):108-15. Pubmed
  3. Stadtler FA, Langner V: The effect of cyproterone and gonadotrophins on the adrenal gland of juvenile and adult rats. A morphological and morphometrical study. Pathol Res Pract. 1985 Mar;179(4-5):493-8. Pubmed
  4. Honer C, Nam K, Fink C, Marshall P, Ksander G, Chatelain RE, Cornell W, Steele R, Schweitzer R, Schumacher C: Glucocorticoid receptor antagonism by cyproterone acetate and RU486. Mol Pharmacol. 2003 May;63(5):1012-20. Pubmed
  5. Holdaway IM, Croxson MS, Evans MC, France J, Sheehan A, Wilson T, Ibbertson HK: Effect of cyproterone acetate on glucocorticoid secretion in patients treated for hirsutism. Acta Endocrinol (Copenh). 1983 Oct;104(2):222-6. Pubmed
External Links
ResourceLink
ChEBI50743
ChEMBLCHEMBL142130
Therapeutic Targets DatabaseDAP000906
PharmGKBPA10049
Drug Product Database704423
WikipediaCyproterone_acetate
ATC CodesG03HA01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Androgen receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Androgen receptor P10275 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Agoulnik IU, Weigel NL: Coactivator selective regulation of androgen receptor activity. Steroids. 2009 Aug;74(8):669-74. Epub 2009 Mar 9. Pubmed
  4. Cabeza M, Flores M, Bratoeff E, de la Pena A, Mendez E, Ceballos G: Intracellular Ca2+ stimulates the binding to androgen receptors in platelets. Steroids. 2004 Oct-Nov;69(11-12):767-72. Pubmed
  5. Sonneveld E, Jansen HJ, Riteco JA, Brouwer A, van der Burg B: Development of androgen- and estrogen-responsive bioassays, members of a panel of human cell line-based highly selective steroid-responsive bioassays. Toxicol Sci. 2005 Jan;83(1):136-48. Epub 2004 Oct 13. Pubmed

Enzymes

1. Cytochrome P450 19A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 19A1 P11511 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

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Drug created on September 26, 2007 09:23 / Updated on March 11, 2014 09:26