Identification

Name
Cyproterone acetate
Accession Number
DB04839
Type
Small Molecule
Groups
Approved, 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.

Structure
Thumb
Synonyms
  • Cyproterone 17-O-acetate
External IDs
NSC-81430 / SH 714
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AndrocurTablet50 mgOralBayer1987-12-31Not applicableCanada
Androcur DepotSolution100 mgIntramuscularBayer1990-12-31Not applicableCanada
CyproteroneTablet50 mgOralBdh Inc.1998-10-082000-08-03Canada
CyproteroneTablet50 mgOralAa Pharma Inc2004-04-20Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Alti-cpaTablet50 mgOralAltimed Pharma Inc.1997-09-222005-05-27Canada
Med-cyproteroneTablet50 mgOralGeneric Medical Partners Inc2012-10-02Not applicableCanada
Mylan-cyproteroneTablet50 mgOralMylan Pharmaceuticals1997-09-192011-03-04Canada
Novo-cyproteroneTablet50 mgOralNovopharm Limited1997-09-172015-10-26Canada
Riva-cyproteroneTablet50 mgOralLaboratoire Riva Inc2012-11-28Not applicableCanada
Riva-cyproterone 50 mgTablet50 mgOralLaboratoire Riva Inc2000-05-122003-07-28Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Cléo -35Cyproterone acetate (2 mg) + Ethinylestradiol (0.035 mg)TabletOralAltius Healthcare Inc2015-10-30Not applicableCanada
Cyestra-35Cyproterone acetate (2 mg) + Ethinylestradiol (0.035 mg)TabletOralPaladin Labs Inc2007-04-03Not applicableCanada
Diane-35Cyproterone acetate (2 mg) + Ethinylestradiol (35 mcg)TabletOralBayer1998-04-08Not applicableCanada
Ran-cyproterone/ethinyl EstradiolCyproterone acetate (2.0 mg) + Ethinylestradiol (0.035 mg)TabletOralRanbaxy Inc.2015-03-26Not applicableCanada
Teva-cyproterone / Ethinyl EstradiolCyproterone acetate (2 mg) + Ethinylestradiol (0.035 mg)TabletOralTeva2008-09-26Not applicableCanada
International/Other Brands
Cyprostat (Bayer)
Categories
UNII
4KM2BN5JHF
CAS number
427-51-0
Weight
Average: 416.938
Monoisotopic: 416.175437123
Chemical Formula
C24H29ClO4
InChI Key
UWFYSQMTEOIJJG-FDTZYFLXSA-N
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
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
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]

Pharmacology

Indication

For the palliative treatment of patients with advanced prostatic carcinoma.

Associated Conditions
Pharmacodynamics

Cyproterone 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 action

The 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.

TargetActionsOrganism
AAndrogen receptor
antagonist
Human
UProstate-specific antigenNot AvailableHuman
Absorption

Completely absorbed following oral administration.

Volume of distribution
Not Available
Protein binding
Not 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.

Route of elimination

It is excreted approximately 60% in the bile and 33% through the kidneys.

Half life

Elimination Following oral or intramuscular administration, the plasma half-life is 38 and 96 hours, respectively.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe serum concentration of (R)-warfarin can be decreased when it is combined with Cyproterone acetate.
(S)-WarfarinCyproterone acetate may decrease the anticoagulant activities of (S)-Warfarin.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Cyproterone acetate.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be decreased when it is combined with Cyproterone acetate.
4-hydroxycoumarinCyproterone acetate may decrease the anticoagulant activities of 4-hydroxycoumarin.
6-O-benzylguanineThe serum concentration of 6-O-benzylguanine can be decreased when it is combined with Cyproterone acetate.
7-DeazaguanineThe serum concentration of 7-Deazaguanine can be decreased when it is combined with Cyproterone acetate.
7,9-DimethylguanineThe serum concentration of 7,9-Dimethylguanine can be decreased when it is combined with Cyproterone acetate.
8-azaguanineThe serum concentration of 8-azaguanine can be decreased when it is combined with Cyproterone acetate.
8-chlorotheophyllineThe serum concentration of 8-chlorotheophylline can be decreased when it is combined with Cyproterone acetate.
Food Interactions
  • Avoid alcohol.
  • Take after a meal.

References

Synthesis Reference

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

US20040024230
General References
  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:4125095]
  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:6237971]
  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:4001026]
  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:12695529]
  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:6227191]
External Links
KEGG Drug
D01368
PubChem Compound
9880
PubChem Substance
46506931
ChemSpider
9496
BindingDB
50094569
ChEBI
50743
ChEMBL
CHEMBL139835
Therapeutic Targets Database
DAP000906
PharmGKB
PA10049
HET
CA4
Wikipedia
Cyproterone_acetate
ATC Codes
G03HB01 — Cyproterone and estrogenG03HA01 — Cyproterone
AHFS Codes
  • 92:92.00 — Other Miscellaneous Therapeutic Agents
PDB Entries
2oz7

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentPolycystic Ovaries Syndrome1
2Active Not RecruitingTreatmentPolycystic Ovarian Syndrome1
2CompletedTreatmentProstate Cancer1
2RecruitingTreatmentPolycystic Ovarian Syndrome1
3Active Not RecruitingTreatmentProstate Cancer1
3CompletedSupportive CareMenopausal Hot Flushes / Prostate Cancer1
3CompletedTreatmentAdenocarcinoma, Prostate1
3CompletedTreatmentProstate Cancer2
3TerminatedTreatmentPedophilia1
3Unknown StatusTreatmentAnxiety Disorders / Long-Term Effects Secondary to Cancer Therapy in Adults / Prostate Cancer / Sexual Dysfunctions / Urinary Complications1
3Unknown StatusTreatmentProstate Cancer2
4CompletedBasic ScienceTranssexualism1
4CompletedTreatmentPolycystic Ovaries Syndrome1
4RecruitingBasic ScienceGender Dysphoria1
4Unknown StatusPreventionHyperandrogenism / Menstrual Irregularities / Polycystic Ovarian Syndrome1
Not AvailableCompletedNot AvailableAcne Vulgaris2
Not AvailableCompletedNot AvailableProstate Cancer1
Not AvailableCompletedTreatmentInsulin Resistance / Polycystic Ovaries Syndrome1
Not AvailableRecruitingBasic SciencePolycystic Ovaries Syndrome1
Not AvailableRecruitingTreatmentHyperandrogenism / Metabolic Cardiovascular Syndrome1
Not AvailableRecruitingTreatmentPolycystic Ovaries Syndrome1
Not AvailableTerminatedNot AvailableProstate Cancer1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionIntramuscular100 mg
TabletOral50 mg
TabletOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)200-201Wiechert, R.; U S . Patent 3,234,093; February 8, 1966; assigned to Schering AG, Germany.
Predicted Properties
PropertyValueSource
Water Solubility0.00152 mg/mLALOGPS
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
Polarizability44.64 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9673
Caco-2 permeable+0.7033
P-glycoprotein substrateSubstrate0.7292
P-glycoprotein inhibitor IInhibitor0.5265
P-glycoprotein inhibitor IINon-inhibitor0.9016
Renal organic cation transporterNon-inhibitor0.8036
CYP450 2C9 substrateNon-substrate0.8
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7834
CYP450 1A2 substrateNon-inhibitor0.8944
CYP450 2C9 inhibitorNon-inhibitor0.7229
CYP450 2D6 inhibitorNon-inhibitor0.8951
CYP450 2C19 inhibitorNon-inhibitor0.737
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8919
Ames testNon AMES toxic0.7067
CarcinogenicityNon-carcinogens0.926
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.8261 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9704
hERG inhibition (predictor II)Non-inhibitor0.6939
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-01t9-3971000000-1dfca0904cf6f0055e70
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Pregnane steroids
Direct Parent
Gluco/mineralocorticoids, progestogins and derivatives
Alternative Parents
Steroid esters / 20-oxosteroids / Halogenated steroids / 3-oxosteroids / Cyclohexenones / Alpha-acyloxy ketones / Carboxylic acid esters / Vinyl chlorides / Monocarboxylic acids and derivatives / Chloroalkenes
show 3 more
Substituents
Progestogin-skeleton / 20-oxosteroid / Steroid ester / 3-oxosteroid / 6-halo-steroid / Halo-steroid / Oxosteroid / Cyclohexenone / Alpha-acyloxy ketone / Ketone
show 15 more
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
acetate ester, 3-oxo Delta(4)-steroid, steroid ester, 20-oxo steroid, chlorinated steroid (CHEBI:50743)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription ...
Gene Name
AR
Uniprot ID
P10275
Uniprot Name
Androgen receptor
Molecular Weight
98987.9 Da
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:17139284]
  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:17016423]
  3. Agoulnik IU, Weigel NL: Coactivator selective regulation of androgen receptor activity. Steroids. 2009 Aug;74(8):669-74. doi: 10.1016/j.steroids.2009.02.007. Epub 2009 Mar 9. [PubMed:19463689]
  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:15579329]
  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:15483189]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Hydrolyzes semenogelin-1 thus leading to the liquefaction of the seminal coagulum.
Specific Function
Endopeptidase activity
Gene Name
KLK3
Uniprot ID
P07288
Uniprot Name
Prostate-specific antigen
Molecular Weight
28741.1 Da
References
  1. Kang Z, Janne OA, Palvimo JJ: Coregulator recruitment and histone modifications in transcriptional regulation by the androgen receptor. Mol Endocrinol. 2004 Nov;18(11):2633-48. Epub 2004 Aug 12. [PubMed:15308689]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name
CYP19A1
Uniprot ID
P11511
Uniprot Name
Aromatase
Molecular Weight
57882.48 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Binkowska M, Woron J: Progestogens in menopausal hormone therapy. Prz Menopauzalny. 2015 Jun;14(2):134-43. doi: 10.5114/pm.2015.52154. Epub 2015 Jun 22. [PubMed:26327902]
  2. NHS [Link]

Drug created on September 26, 2007 09:23 / Updated on October 16, 2018 08:37