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Identification
Name Danazol
Accession Number DB01406
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Anatrol
Chronogyn
Cyclomen
Danocrine
Brand mixtures Not Available
Categories
  • Estrogen Antagonists
CAS number 17230-88-5
Weight Average: 337.4553
Monoisotopic: 337.204179113
Chemical Formula C22H27NO2
InChI Key InChIKey=POZRVZJJTULAOH-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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Steroids and Steroid Derivatives
Substructures
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Alkynes
  • Steroids and Steroid Derivatives
  • Isoxazoles
  • Alcohols and Polyols
  • Heterocyclic compounds
  • Aromatic compounds
  • Oxazoles
Pharmacology
Indication For 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.
Pharmacodynamics Danazol 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 action As 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)
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism Hepatic, to principal metabolites, ethisterone and 17-hydroxymethylethisterone.
Route of elimination Not Available
Half life Approximately 24 hours.
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • American therapeutics inc
  • Barr laboratories inc
  • Lannett holdings inc
  • Sanofi aventis us llc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Prices
Unit description Cost Unit
Danazol powder 21.42 USD g
Danazol 200 mg capsule 5.2 USD capsule
Danocrine 200 mg capsule 4.53 USD capsule
Danazol 100 mg capsule 2.92 USD capsule
Cyclomen 200 mg Capsule 2.31 USD capsule
Danazol 50 mg capsule 1.95 USD capsule
Cyclomen 100 mg Capsule 1.45 USD capsule
Cyclomen 50 mg Capsule 0.98 USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 225.6 °C PhysProp
logP 0.51 PERRISSOUD,D & TESTA,B (1986)
Predicted Properties
Property Value Source
water solubility 1.76e-02 g/l ALOGPS
logP 3.62 ALOGPS
logP 3.46 ChemAxon
logS -4.3 ALOGPS
pKa (strongest acidic) 17.59 ChemAxon
pKa (strongest basic) 0.25 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 46.26 ChemAxon
rotatable bond count 0 ChemAxon
refractivity 98.54 ChemAxon
polarizability 38.56 ChemAxon
References
Synthesis Reference Not Available
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
Resource Link
KEGG Drug D00289 Link_out
PubChem Compound 28417 Link_out
PubChem Substance 46506475 Link_out
ChemSpider 26436 Link_out
ChEBI 4315 Link_out
ChEMBL 4315 Link_out
Therapeutic Targets Database DAP001017 Link_out
PharmGKB PA164749056 Link_out
Drug Product Database 2018144 Link_out
RxList http://www.rxlist.com/cgi/generic/danazol.htm Link_out
Drugs.com http://www.drugs.com/cdi/danazol.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Danazol Link_out
ATC Codes
  • G03XA01
AHFS Codes
  • 68:08.00
PDB Entries Not Available
FDA label Not Available
MSDS show (75 KB)
Interactions
Drug Interactions
Drug Interaction
Acenocoumarol The androgen, danazol, may increase the anticoagulant effect of acenocoumarol.
Anisindione The androgen, danazol, may increase the anticoagulant effect of anisindione.
Carbamazepine Danazol 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.
Cyclosporine The androgen, danazol, may increase the effect and toxicity of cyclosporine.
Dicumarol The androgen, danazol, may increase the anticoagulant effect of dicumarol.
Lovastatin Risk of severe myopathy/rhabdomyolysis with this combination
Tacrolimus Danazol 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.
Warfarin Danazol 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

Pharmacological action: yes
Actions: agonist

Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues

Organism class: human
UniProt ID: P03372 Link_out
Gene: ESR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: agonist

The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Activated, but not phosphorylated, by HIPK3

Organism class: human
UniProt ID: P10275 Link_out
Gene: AR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: agonist

The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues

Organism class: human
UniProt ID: P06401 Link_out
Gene: PGR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: negative modulator

Receptor for gonadotropin releasing hormone (GnRH) that mediate the action of GnRH to stimulate the secretion of the gonadotropic hormones (LH and FSH). This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Isoform 2 may act a an inhibitor of GnRH-R signaling

Organism class: human
UniProt ID: P30968 Link_out
Gene: GNRHR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Gonadotropin-releasing hormone II receptor

Pharmacological action: yes
Actions: negative modulator

Receptor for gonadotropin releasing hormone II (GnRH II). This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system (Potential)

Organism class: human
UniProt ID: Q96P88 Link_out
Gene: GNRHR2 Link_out
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Small inducible cytokine A2

Pharmacological action: unknown
Actions: inhibitor

Chemotactic factor that attracts monocytes and basophils but not neutrophils or eosinophils. Augments monocyte anti-tumor activity. Has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis or atherosclerosis. May be involved in the recruitment of monocytes into the arterial wall during the disease process of atherosclerosis

Organism class: human
UniProt ID: P13500 Link_out
Gene: CCL2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Catalyzes the formation of aromatic C18 estrogens from C19 androgens

UniProt ID: P11511 Link_out
Gene: CYP19A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration

UniProt ID: P04278 Link_out
Gene: SHBG Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on July 13, 2007 14:36 / Updated on February 08, 2013 16:20