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Identification
NameDanazol
Accession NumberDB01406
TypeSmall Molecule
GroupsApproved
Description

A synthetic steroid with antigonadotropic and anti-estrogenic activities that acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. Danazol has been used in the treatment of endometriosis and some benign breast disorders. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
CyclomenNot AvailableNot Available
DanazolumNot AvailableNot Available
DanocrineNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
CyclomenSanofi
DanocrineSanofi
DanolSanofi
Brand mixturesNot Available
CategoriesNot Available
CAS number17230-88-5
WeightAverage: 337.4553
Monoisotopic: 337.204179113
Chemical FormulaC22H27NO2
InChI KeyPOZRVZJJTULAOH-LHZXLZLDSA-N
InChI
InChI=1S/C22H27NO2/c1-4-22(24)10-8-18-16-6-5-15-11-19-14(13-23-25-19)12-20(15,2)17(16)7-9-21(18,22)3/h1,11,13,16-18,24H,5-10,12H2,2-3H3/t16-,17+,18+,20+,21+,22+/m1/s1
IUPAC Name
(1S,2R,13R,14S,17R,18S)-17-ethynyl-2,18-dimethyl-7-oxa-6-azapentacyclo[11.7.0.0^{2,10}.0^{4,8}.0^{14,18}]icosa-4(8),5,9-trien-17-ol
SMILES
[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC3=C(C[C@]12C)C=NO3
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassAndrogens and Derivatives
Direct parentAndrogens and Derivatives
Alternative parentsHydroxysteroids; Ynones; Tertiary Alcohols; Isoxazoles; Cyclic Alcohols and Derivatives; Polyamines
Substituentsynone; cyclic alcohol; azole; isoxazole; tertiary alcohol; polyamine; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the androgens and derivatives. These are hydroxylated C19 steroid hormones. They are known to favour the development of masculine characteristics. They also show profound effects on scalp and body hair in humans.
Pharmacology
IndicationFor the treatment of endometriosis and fibrocystic breast disease (in patients unresponsive to simple measures). Also used for the prophylactic treatment of all types of hereditary angioedema in males and females.
PharmacodynamicsDanazol is a derivative of the synthetic steroid ethisterone, a modified testosterone. It was approved by the U.S. Food and Drug Administration (FDA) as the first drug to specifically treat endometriosis, but its role as a treatment for endometriosis has been largely replaced by the gonadotropin-releasing hormone (GnRH) agonists. Danazol has antigonadotropic and anti-estrogenic activities. Danazol acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties.
Mechanism of actionAs a gonadotropin inhibitor, danazol suppresses the pituitary-ovarian axis possibly by inhibiting the output of pituitary gonadotropins. Danazol also depresses the preovulatory surge in output of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), thereby reducing ovarian estrogen production. Danazol may also directly inhibits ovarian steroidogenesis; bind to androgen, progesterone, and glucocorticoid receptors; bind to sex-hormone-binding globulin and corticosteroid-binding globulin; and increases the metabolic clearance rate of progesterone. Another mechanism of action by which danazol may use to facilitate regression of endometriosis is by decreasing IgG, IgM, and IgA concentrations, as well as phospholipid and IgG isotope autoantibodies. In the treatment of endometriosis, as a consequence of suppression of ovarian function, danazol causes both normal and ectopic endometrial tissues to become inactive and atrophic. This leads to anovulation and associated amenorrhea. In fibrocystic breast disease, the exact mechanism of action of danazol is unknown, but may be related to suppressed estrogenic stimulation as a result of decreased ovarian production of estrogen. A direct effect on steroid receptor sites in breast tissue is also possible. This leads to a disappearance of nodularity, relief of pain and tenderness, and possibly changes in the menstrual pattern. In terms of hereditary angioedema, danazol corrects the underlying biochemical deficiency by increasing serum concentrations of the deficient C1 esterase inhibitor, resulting in increased serum concentrations of the C4 component of the complement system. (Source: PharmGKB)
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic, to principal metabolites, ethisterone and 17-hydroxymethylethisterone.

SubstrateEnzymesProduct
Danazol
Not Available
17-hydroxymethylethisteroneDetails
Danazol
Not Available
EthisteroneDetails
Route of eliminationNot Available
Half lifeApproximately 24 hours.
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 + 0.9781
Caco-2 permeable + 0.8866
P-glycoprotein substrate Substrate 0.5938
P-glycoprotein inhibitor I Non-inhibitor 0.5194
P-glycoprotein inhibitor II Non-inhibitor 0.8893
Renal organic cation transporter Non-inhibitor 0.8178
CYP450 2C9 substrate Non-substrate 0.8487
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Substrate 0.67
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Non-inhibitor 0.7407
CYP450 2D6 substrate Non-inhibitor 0.8731
CYP450 2C19 substrate Inhibitor 0.5962
CYP450 3A4 substrate Inhibitor 0.796
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7692
Ames test Non AMES toxic 0.6885
Carcinogenicity Non-carcinogens 0.9083
Biodegradation Not ready biodegradable 0.9562
Rat acute toxicity 1.3291 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.6896
hERG inhibition (predictor II) Non-inhibitor 0.8734
Pharmacoeconomics
Manufacturers
  • American therapeutics inc
  • Barr laboratories inc
  • Lannett holdings inc
  • Sanofi aventis us llc
Packagers
Dosage forms
FormRouteStrength
CapsuleOral
Prices
Unit descriptionCostUnit
Danazol powder21.42USDg
Danazol 200 mg capsule5.2USDcapsule
Danocrine 200 mg capsule4.53USDcapsule
Danazol 100 mg capsule2.92USDcapsule
Cyclomen 200 mg Capsule2.31USDcapsule
Danazol 50 mg capsule1.95USDcapsule
Cyclomen 100 mg Capsule1.45USDcapsule
Cyclomen 50 mg Capsule0.98USDcapsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point224.2-226.8Clinton, R. and Hanson, A.; US. Patent 3,135,743; June 2, 1964; assigned to Sterling Drug.
logP0.51PERRISSOUD,D & TESTA,B (1986)
Predicted Properties
PropertyValueSource
Water Solubility0.0176ALOGPS
logP3.62ALOGPS
logP3.46ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)17.59ChemAxon
pKa (Strongest Basic)0.25ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area46.26 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity98.54 m3·mol-1ChemAxon
Polarizability38.56 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraMS/MS1D NMR2D NMR
References
Synthesis Reference

Clinton, R. and Hanson, A.; US. Patent 3,135,743; June 2, 1964; assigned to Sterling Drug.

General Reference
  1. Dmowski WP: Danazol. A synthetic steroid with diverse biologic effects. J Reprod Med. 1990 Jan;35(1 Suppl):69-74; discussion 74-5. Pubmed
  2. Donaldson VH: Danazol. Am J Med. 1989 Sep;87(3N):49N-55N. Pubmed
  3. Jenkin G: Review: The mechanism of action of danazol, a novel steroid derivative. Aust N Z J Obstet Gynaecol. 1980 May;20(2):113-8. Pubmed
External Links
ResourceLink
KEGG DrugD00289
PubChem Compound28417
PubChem Substance46506475
ChemSpider26436
ChEBI4315
ChEMBLCHEMBL1479
Therapeutic Targets DatabaseDAP001017
PharmGKBPA164749056
Drug Product Database2018144
RxListhttp://www.rxlist.com/cgi/generic/danazol.htm
Drugs.comhttp://www.drugs.com/cdi/danazol.html
WikipediaDanazol
ATC CodesG03XA01
AHFS Codes
  • 68:08.00
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(75 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolThe androgen, danazol, may increase the anticoagulant effect of acenocoumarol.
AnisindioneThe androgen, danazol, may increase the anticoagulant effect of anisindione.
CarbamazepineDanazol may decrease the metabolism of carbamazepine. Monitor for changes in the therapeutic and adverse effects of carbamazepine if danazol is initiated, discontinued or dose changed.
CyclosporineThe androgen, danazol, may increase the effect and toxicity of cyclosporine.
DicoumarolThe androgen, danazol, may increase the anticoagulant effect of dicumarol.
ExenatideMonitor therapy due to reduced hypoglycemic effect of exenatide.
Insulin AspartMonitor therapy due to decreased hypoglycemic effect of insulin aspart.
LovastatinRisk of severe myopathy/rhabdomyolysis with this combination
TacrolimusDanazol may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Danazol therapy is initiated, discontinued or altered.
WarfarinDanazol may increase the serum concentration and anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if danazol is initiated, discontinued or dose changed.
Food Interactions
  • Take without regard to meals.

Targets

1. Estrogen receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Estrogen receptor P03372 Details

References:

  1. Fujimoto J, Hori M, Itoh T, Ichigo S, Nishigaki M, Tamaya T: Danazol decreases transcription of estrogen receptor gene in human monocytes. Gen Pharmacol. 1995 May;26(3):507-16. Pubmed
  2. Snyder BW, Beecham GD, Winneker RC: Danazol suppression of luteinizing hormone in the rat: evidence for mediation by both androgen and estrogen receptors. Proc Soc Exp Biol Med. 1990 May;194(1):54-7. Pubmed
  3. Sanfilippo JS, Barrows GH, Apkarian RP, Wittliff JL: Evaluation of danazol influence upon the uterus using scanning electron microscopic morphometric and biochemical analyses. Surg Gynecol Obstet. 1985 May;160(5):421-8. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Androgen receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Androgen receptor P10275 Details

References:

  1. Donaldson VH: Danazol. Am J Med. 1989 Sep;87(3N):49N-55N. Pubmed
  2. Sasagawa S, Shimizu Y, Kami H, Takeuchi T, Mita S, Imada K, Kato S, Mizuguchi K: Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharmacokinetic profile. Steroids. 2008 Feb;73(2):222-31. Epub 2007 Oct 22. Pubmed
  3. Gomez F, Ruiz P, Lopez R, Rivera C, Romero S, Bernal JA: Effects of androgen treatment on expression of macrophage Fcgamma receptors. Clin Diagn Lab Immunol. 2000 Jul;7(4):682-6. Pubmed
  4. Roselli CE: The effect of anabolic-androgenic steroids on aromatase activity and androgen receptor binding in the rat preoptic area. Brain Res. 1998 May 11;792(2):271-6. Pubmed
  5. Dmowski WP: Danazol. A synthetic steroid with diverse biologic effects. J Reprod Med. 1990 Jan;35(1 Suppl):69-74; discussion 74-5. Pubmed

3. Progesterone receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Progesterone receptor P06401 Details

References:

  1. Beaumont H, Augood C, Duckitt K, Lethaby A: Danazol for heavy menstrual bleeding. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD001017. Pubmed
  2. Sasagawa S, Shimizu Y, Kami H, Takeuchi T, Mita S, Imada K, Kato S, Mizuguchi K: Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharmacokinetic profile. Steroids. 2008 Feb;73(2):222-31. Epub 2007 Oct 22. Pubmed
  3. Huang HF, Wang M: [Effects of gossypol acetate, danazol, progesterone and GnRH-A on estrogen and progesterone receptors of human endometrial cells] Zhongguo Zhong Xi Yi Jie He Za Zhi. 1994 Jun;14(6):352-3, 325. Pubmed
  4. Dmowski WP: Danazol. A synthetic steroid with diverse biologic effects. J Reprod Med. 1990 Jan;35(1 Suppl):69-74; discussion 74-5. Pubmed

4. Gonadotropin-releasing hormone receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: negative modulator

Components

Name UniProt ID Details
Gonadotropin-releasing hormone receptor P30968 Details

References:

  1. Tian ZZ, Zhao H, Chen BY: [Effect of Chinese herbal medicine for nourishing yin and purging fire on mRNA expressions of gonadotropin-releasing hormone and its receptor in precocious puberty model rats] Zhongguo Zhong Xi Yi Jie He Za Zhi. 2003 Sep;23(9):695-8. Pubmed
  2. Menon M, Peegel H, Katta V: Inhibition of gonadotropin-releasing hormone receptors in rat anterior pituitary monolayer cell cultures by danazol. Am J Obstet Gynecol. 1986 Feb;154(2):367-72. Pubmed
  3. Roth C, Hegemann F, Hildebrandt J, Balzer I, Witt A, Wuttke W, Jarry H: Pituitary and gonadal effects of GnRH (gonadotropin releasing hormone) analogues in two peripubertal female rat models. Pediatr Res. 2004 Jan;55(1):126-33. Epub 2003 Nov 6. Pubmed
  4. Dmowski WP: Danazol. A synthetic steroid with diverse biologic effects. J Reprod Med. 1990 Jan;35(1 Suppl):69-74; discussion 74-5. Pubmed

5. Putative gonadotropin-releasing hormone II receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: negative modulator

Components

Name UniProt ID Details
Putative gonadotropin-releasing hormone II receptor Q96P88 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. Dmowski WP: Danazol. A synthetic steroid with diverse biologic effects. J Reprod Med. 1990 Jan;35(1 Suppl):69-74; discussion 74-5. Pubmed
  4. Menon M, Peegel H, Katta V: Inhibition of gonadotropin-releasing hormone receptors in rat anterior pituitary monolayer cell cultures by danazol. Am J Obstet Gynecol. 1986 Feb;154(2):367-72. Pubmed

6. C-C motif chemokine 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
C-C motif chemokine 2 P13500 Details

References:

  1. Boucher A, Lemay A, Akoum A: Effect of hormonal agents on monocyte chemotactic protein-1 expression by endometrial epithelial cells of women with endometriosis. Fertil Steril. 2000 Nov;74(5):969-75. Pubmed
  2. Jolicoeur C, Lemay A, Akoum A: Comparative effect of danazol and a GnRH agonist on monocyte chemotactic protein-1 expression by endometriotic cells. Am J Reprod Immunol. 2001 Feb;45(2):86-93. 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

2. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 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

Carriers

1. Sex hormone-binding globulin

Kind: protein

Organism: Human

Pharmacological action: yes

Components

Name UniProt ID Details
Sex hormone-binding globulin P04278 Details

References:

  1. De Leo V, Morgante G, La Marca A, Musacchio MC, Sorace M, Cavicchioli C, Petraglia F: A benefit-risk assessment of medical treatment for uterine leiomyomas. Drug Saf. 2002;25(11):759-79. Pubmed
  2. Telimaa S, Apter D, Reinila M, Ronnberg L, Kauppila A: Placebo-controlled comparison of hormonal and biochemical effects of danazol and high-dose medroxyprogesterone acetate. Eur J Obstet Gynecol Reprod Biol. 1990 Jul-Aug;36(1-2):97-105. Pubmed
  3. Donaldson VH: Danazol. Am J Med. 1989 Sep;87(3N):49N-55N. Pubmed
  4. Valimaki M, Nilsson CG, Roine R, Ylikorkala O: Comparison between the effects of nafarelin and danazol on serum lipids and lipoproteins in patients with endometriosis. J Clin Endocrinol Metab. 1989 Dec;69(6):1097-103. Pubmed
  5. Forbes KL, Dowsett M, Rose GL, Mudge JE, Jeffcoate SL: Dosage-related effects of danazol on sex hormone binding globulin and free and total androgen levels. Clin Endocrinol (Oxf). 1986 Nov;25(5):597-605. Pubmed

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Drug created on July 13, 2007 14:36 / Updated on April 10, 2014 11:43