CYPROTERONE ACETATE

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H29ClO4
Molecular Weight	416.9385
Optical Activity	UNSPECIFIED
Defined Stereocenters	8 / 8
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(=O)[C@]1(CC[C@@]2([H])[C@]3([H])C=C(C4=CC(=O)[C@]5([H])C[C@]5([H])[C@]4(C)[C@@]3([H])CC[C@@]21C)Cl)OC(=O)C

InChI

InChIKey=UWFYSQMTEOIJJG-FDTZYFLXSA-N

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

HIDE SMILES / InChI

Description
Sources: http://www.yourcontraception.com/index2.php?option=com_content&do_pdf=1&id=72

Cyproterone acetate is a steroid drug which was developed by Schering A.G (now Bayer). Cyproterone acetate was approved in Canada, Asia, Latin America and Europe for the treatment of sever acne under the name Diane-35 (ethinyl estradiol) and its mechanism of action in this condition is explained by competitive inhibition of androgen receptor AR. In Canada cyproterone acetate is widely used as a contraceptive, however its usage is associated with liver toxicity and clots formation. In the UK the drug is marketed for the treatment of prostate cancer (Cyproterone acetate brand name).

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Androgen Receptor 163 Target ID: CHEMBL1871 Sources: http://www.pharmaline.co.il/images/newsletterregistration/bayer/11022011/dianedr.pdf	Antagonist 2575		4.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Severe acne 1 Sources: http://e-lactancia.org/media/papers/Diane-PM-Bayer2014.pdf	Curative		Approved 8043	DIANE-35 Approved Use DIANE-35 (cyproterone acetate and ethinyl estradiol) is indicated for the treatment of women with severe acne, with associated symptoms of androgenization, including seborrhea and mild hirsutism.
Prostate cancer 159 Sources: http://www.stragenuk.com/pdf/PIL-November-2016-2.pdf	Primary		Approved 8043	CYPROTERONE ACETATE Approved Use Cyproterone Acetate tablets are used in men to treat prostate cancer

C_max

Value	Dose	Co-administered	Analyte	Population
406 ng/mL DRUG LABEL https://www.bayer.ca/omr/online/androcur-pm-en.pdf	300 mg 1 times / week steady-state, intramuscular dose: 300 mg route of administration: Intramuscular experiment type: STEADY-STATE co-administered:		CYPROTERONE ACETATE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
70 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/6458025	300 mg 1 times / week steady-state, intramuscular dose: 300 mg route of administration: Intramuscular experiment type: STEADY-STATE co-administered:		CYPROTERONE ACETATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.9 day DRUG LABEL https://www.bayer.ca/omr/online/androcur-pm-en.pdf	300 mg 1 times / week steady-state, intramuscular dose: 300 mg route of administration: Intramuscular experiment type: STEADY-STATE co-administered:		CYPROTERONE ACETATE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
200 mg 1 times / day multiple, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Co-administed with:: LHRH analogue(monthly depot injections) Sources: https://pubmed.ncbi.nlm.nih.gov/19249153/	unhealthy, Mean age 72.6 years n = 293 Health Status: unhealthy Condition: prostate cancer Age Group: Mean age 72.6 years Sex: M Population Size: 293 Sources: https://pubmed.ncbi.nlm.nih.gov/19249153/	Other AEs: Hot flushes, Gynaecomastia... Other AEs: Hot flushes (30%) Gynaecomastia (19.5%) Headache (12.3%) Skin and subcutaneous tissue disorders NEC (6.8%) Sources: https://pubmed.ncbi.nlm.nih.gov/19249153/
100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2946604/	unhealthy, adult n = 76 Health Status: unhealthy Condition: hirsutism Age Group: adult Sex: F Population Size: 76 Sources: https://pubmed.ncbi.nlm.nih.gov/2946604/	Disc. AE: Depression, Weight increase... Other AEs: Amenorrhea, Weight gain... AEs leading to discontinuation/dose reduction: Depression Weight increase Headache Libido decreased Fatigue (6.7%) Other AEs: Amenorrhea (32.6%) Weight gain Sources: https://pubmed.ncbi.nlm.nih.gov/2946604/
600 mg 1 times / day multiple, oral Highest studied dose Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9337516/ https://pubmed.ncbi.nlm.nih.gov/11393581/	unhealthy, children Health Status: unhealthy Condition: precocious puberty Age Group: children Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/9337516/ https://pubmed.ncbi.nlm.nih.gov/11393581/	Sources: https://pubmed.ncbi.nlm.nih.gov/9337516/ https://pubmed.ncbi.nlm.nih.gov/11393581/
300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2009-PI-01092-3&d=202012161016933	unhealthy Health Status: unhealthy Sex: M Sources: https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2009-PI-01092-3&d=202012161016933	Sources: https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2009-PI-01092-3&d=202012161016933

AEs

AE	Significance	Dose	Population
Headache	12.3%	200 mg 1 times / day multiple, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Co-administed with:: LHRH analogue(monthly depot injections) Sources: https://pubmed.ncbi.nlm.nih.gov/19249153/	unhealthy, Mean age 72.6 years n = 293 Health Status: unhealthy Condition: prostate cancer Age Group: Mean age 72.6 years Sex: M Population Size: 293 Sources: https://pubmed.ncbi.nlm.nih.gov/19249153/
Gynaecomastia	19.5%	200 mg 1 times / day multiple, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Co-administed with:: LHRH analogue(monthly depot injections) Sources: https://pubmed.ncbi.nlm.nih.gov/19249153/	unhealthy, Mean age 72.6 years n = 293 Health Status: unhealthy Condition: prostate cancer Age Group: Mean age 72.6 years Sex: M Population Size: 293 Sources: https://pubmed.ncbi.nlm.nih.gov/19249153/
Hot flushes	30%	200 mg 1 times / day multiple, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Co-administed with:: LHRH analogue(monthly depot injections) Sources: https://pubmed.ncbi.nlm.nih.gov/19249153/	unhealthy, Mean age 72.6 years n = 293 Health Status: unhealthy Condition: prostate cancer Age Group: Mean age 72.6 years Sex: M Population Size: 293 Sources: https://pubmed.ncbi.nlm.nih.gov/19249153/
Skin and subcutaneous tissue disorders NEC	6.8%	200 mg 1 times / day multiple, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Co-administed with:: LHRH analogue(monthly depot injections) Sources: https://pubmed.ncbi.nlm.nih.gov/19249153/	unhealthy, Mean age 72.6 years n = 293 Health Status: unhealthy Condition: prostate cancer Age Group: Mean age 72.6 years Sex: M Population Size: 293 Sources: https://pubmed.ncbi.nlm.nih.gov/19249153/
Weight gain		100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2946604/	unhealthy, adult n = 76 Health Status: unhealthy Condition: hirsutism Age Group: adult Sex: F Population Size: 76 Sources: https://pubmed.ncbi.nlm.nih.gov/2946604/
Amenorrhea	32.6%	100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2946604/	unhealthy, adult n = 76 Health Status: unhealthy Condition: hirsutism Age Group: adult Sex: F Population Size: 76 Sources: https://pubmed.ncbi.nlm.nih.gov/2946604/
Fatigue	6.7% Disc. AE	100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2946604/	unhealthy, adult n = 76 Health Status: unhealthy Condition: hirsutism Age Group: adult Sex: F Population Size: 76 Sources: https://pubmed.ncbi.nlm.nih.gov/2946604/
Depression	Disc. AE	100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2946604/	unhealthy, adult n = 76 Health Status: unhealthy Condition: hirsutism Age Group: adult Sex: F Population Size: 76 Sources: https://pubmed.ncbi.nlm.nih.gov/2946604/
Headache	Disc. AE	100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2946604/	unhealthy, adult n = 76 Health Status: unhealthy Condition: hirsutism Age Group: adult Sex: F Population Size: 76 Sources: https://pubmed.ncbi.nlm.nih.gov/2946604/
Libido decreased	Disc. AE	100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2946604/	unhealthy, adult n = 76 Health Status: unhealthy Condition: hirsutism Age Group: adult Sex: F Population Size: 76 Sources: https://pubmed.ncbi.nlm.nih.gov/2946604/
Weight increase	Disc. AE	100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2946604/	unhealthy, adult n = 76 Health Status: unhealthy Condition: hirsutism Age Group: adult Sex: F Population Size: 76 Sources: https://pubmed.ncbi.nlm.nih.gov/2946604/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1601 inhibitor 1467	inhibitor 1604	inhibitor 1702

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B3 657 OATP1B1 733 CYP2C8 818 CYP2C19 1325 P-gp 1330 MRP2 346		CYP1A2 637 CYP2E1 117

Drug as perpetrator

Target	Modality	Activity
OATP1B1 748	inhibitor 3045 Sources: https://molpharm.aspetjournals.org/content/83/6/1257 Page: -	no [Inhibition 10 uM]
OATP1B3 666	inhibitor 3045 Sources: https://molpharm.aspetjournals.org/content/83/6/1257 Page: -	no
P-gp 1514	inhibitor 3045 Sources: https://dmd.aspetjournals.org/content/34/2/203 Page: -	yes [IC50 4.3 uM]
CYP1A2 1532	inducer 1440 Sources: https://pdf.hres.ca/dpd_pm/00011374.PDF#page=10 Page: 10.0	yes
CYP2C19 1392	inhibitor 3045 Sources: https://pdf.hres.ca/dpd_pm/00011374.PDF#page=10 Page: 10.0	yes
CYP2C8 865	inhibitor 3045 Sources: https://pdf.hres.ca/dpd_pm/00011374.PDF#page=10 Page: 10.0	yes
CYP2C9 1648	inhibitor 3045 Sources: https://pdf.hres.ca/dpd_pm/00011374.PDF#page=10 Page: 10.0	yes
CYP2D6 1738	inhibitor 3045 Sources: https://pdf.hres.ca/dpd_pm/00011374.PDF#page=10 Page: 10.0	yes
CYP2E1 871	inducer 1440 Sources: https://pdf.hres.ca/dpd_pm/00011374.PDF#page=10 Page: 10.0	yes
CYP3A4 1772	inhibitor 3045 Sources: https://pdf.hres.ca/dpd_pm/00011374.PDF#page=10 Page: 10.0	yes
MRP2 434	inhibitor 3045 Sources: https://dmd.aspetjournals.org/content/33/11/1576 Page: -	yes
PXR 43	activator 202 Sources: https://www.tandfonline.com/doi/abs/10.1517/17425255.1.4.641 Page: -	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1601	substrate 3113 Sources: https://pdf.hres.ca/dpd_pm/00011374.PDF#page=10 Page: 10.0	yes

PubMed

Title	Date	PubMed
[Prevention of testosterone-vasopressin induced necrosis of the kidney cortex by cyproterone acetate].	1979 Jul	503094
Effect of cyproterone acetate on glucocorticoid secretion in patients treated for hirsutism.	1983 Oct	6227191
Cardiovascular side effects of diethylstilbestrol, cyproterone acetate, medroxyprogesterone acetate and estramustine phosphate used for the treatment of advanced prostatic cancer: results from European Organization for Research on Treatment of Cancer trials 30761 and 30762.	1986 Feb	2935644
Pulmonary embolism after short-term treatment of acne vulgaris with ovulation suppressor agents.	1986 Oct 6	2945082
Comparison of diethylstilbestrol, cyproterone acetate and medroxyprogesterone acetate in the treatment of advanced prostatic cancer: final analysis of a randomized phase III trial of the European Organization for Research on Treatment of Cancer Urological Group.	1986 Sep	2942707
Fulminant hepatitis due to cyproterone acetate.	1989 Jan 28	2563116
Effects of hypolipidemic drugs nafenopin and clofibrate on phenotypic expression and cell death (apoptosis) in altered foci of rat liver.	1990 Apr	1691053
Induction of dorsolateral prostate adenocarcinomas and other accessory sex gland lesions in male Wistar rats by a single administration of N-methyl-N-nitrosourea, 7,12-dimethylbenz(a)anthracene, and 3,2'-dimethyl-4-aminobiphenyl after sequential treatment with cyproterone acetate and testosterone propionate.	1990 Feb 1	2137026
Severe hepatitis caused by cyproterone acetate.	1990 May	2140997
Hepatocellular carcinoma after treatment with cyproterone acetate combined with ethinyloestradiol.	1995 Feb 18	7853970
Severe hepatitis and liver failure induced by cyproterone acetate.	1996 Oct	8958378
Environmental xenobiotics and the antihormones cyproterone acetate and spironolactone use the nuclear hormone pregnenolone X receptor to activate the CYP3A23 hormone response element.	1998 Dec	9855641
Synthesis and biological activity of a novel series of nonsteroidal, peripherally selective androgen receptor antagonists derived from 1,2-dihydropyridono[5,6-g]quinolines.	1998 Feb 12	9484511
Rapid and sensitive reporter gene assays for detection of antiandrogenic and estrogenic effects of environmental chemicals.	1999 Mar 1	10053169
The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism.	2002 Oct	12372848
Differential expression of c-fos and c-myc protooncogenes by estrogens, xenobiotics and other growth-stimulatory agents in primary rat hepatocytes.	2003 Mar	12632255
Glucocorticoid receptor antagonism by cyproterone acetate and RU486.	2003 May	12695529
Study of 202 natural, synthetic, and environmental chemicals for binding to the androgen receptor.	2003 Oct	14565775
Partial agonist/antagonist properties of androstenedione and 4-androsten-3beta,17beta-diol.	2004 Aug	15336702
Coregulator recruitment and histone modifications in transcriptional regulation by the androgen receptor.	2004 Nov	15308689
Influence of exogenous oestrogen or (anti-) androgen administration on soluble transferrin receptor in human plasma.	2005 Jul	16002536
Receptor isoform and ligand-specific modulation of dihydrotestosterone-induced prostate specific antigen gene expression and prostate tumor cell growth by estrogens.	2005 Jul-Aug	15955889
In silico prediction of pregnane X receptor activators by machine learning approaches.	2007 Jan	17003167
Ligand-specific dynamics of the androgen receptor at its response element in living cells.	2007 Mar	17189428
Screening of 397 chemicals and development of a quantitative structure--activity relationship model for androgen receptor antagonism.	2008 Apr	18324785
Testosterone-induced modulation of nitric oxide-cGMP signaling pathway and androgenesis in the rat Leydig cells.	2010 Sep	20463352
Abrupt regression of a meningioma after discontinuation of cyproterone treatment.	2010 Sep	20053802
Anabolic-androgenic steroids induce apoptosis and NOS2 (nitric-oxide synthase 2) in adult rat Leydig cells following in vivo exposure.	2012 Dec	23085480
Bisphenol A affects androgen receptor function via multiple mechanisms.	2013 May 25	23562765
Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action.	2014	25058030

Patents

Sample Use Guides

In Vivo Use Guide

Acne: 1 tablet containing 2 mg cyproterone acetate and 0.035 mg ethinyl estradiol is taken daily for 21 consecutive days beginning on day 1 of the menstrual cycle. The tablets are then discontinued for 7 days and the cycle repeats. Prostatic cancer: the usual dose range is from 1 tablet once a day (100mg) up to 1 tablet three times a day (300mg).

Route of Administration: Oral

In Vitro Use Guide

Primary explants (approx. 1 mm3) of prostate tissue from patients with benign prostatic hyperplasia were treated with 10 nM dihydrotestosterone, 50 pM diethylstilbestrol and 100 nM cyproterone acetate to test steroids action on oxytocin secretion.

Name

Type

Language

CYPROTERONE ACETATE

Official Name

English

CYPROTERONE ACETATE [WHO-DD]

Common Name

English

CYPROTERONE ACETATE [EP MONOGRAPH]

Common Name

English

CYPROTERONE ACETATE [JAN]

Common Name

English

NSC-81430

Code

English

CYPROTERONE ACETATE [HSDB]

Common Name

English

CYPROTERONE ACETATE [USAN]

Common Name

English

SH-714

Code

English

CYPROSTAT

Brand Name

English

CYPROTERONE ACETATE [MI]

Common Name

English

ANDROCUR

Brand Name

English

6-CHLORO-1.BETA.,2.BETA.-DIHYDRO-17-HYDROXY-3'H-CYCLOPROPA(1,2)-PREGNA-1,4,6-TRIENE-3,20-DIONE ACETATE

Common Name

English

CYPROTERONE ACETATE [MART.]

Common Name

English

SH 714

Code

English

3'H-CYCLOPROPA(1,2)PREGNA-1,4,6-TRIENE-3,20-DIONE, 17-(ACETYLOXY)-6-CHLORO-1,2-DIHYDRO-, (1.BETA.,2.BETA.)-

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

3884