DANAZOL

First approved in 1976

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H27NO2
Molecular Weight	337.4553
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@@]3([H])[C@@]2([H])CCC4=CC5=C(C[C@]34C)C=NO5

InChI

InChIKey=POZRVZJJTULAOH-LHZXLZLDSA-N

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

HIDE SMILES / InChI

Description
Sources: http://products.sanofi.ca/en/cyclomen.pdf
Curator's Comment: description was created based on several sources, including https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f2c9b713-aafc-49ca-866e-334d9b5c2e2d, www.ncbi.nlm.nih.gov/pubmed/1606119

Danazol is a synthetic derivative of ethisterone which is approved by FDA for the treatment of endometriosis, fibrocystic breast disease and for preventing hereditary angioedema. It is believed that the in vivo therapeutic effect is achieved through activating androgen receptors. Danazol has teratogenic effects.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Androgen Receptor 167 Target ID: CHEMBL1871 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f2c9b713-aafc-49ca-866e-334d9b5c2e2d	Agonist 2678

Conditions

Condition	Modality	Highest Phase	Product
Endometriosis 32 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f2c9b713-aafc-49ca-866e-334d9b5c2e2d	Primary	Approved 8429	DANAZOL Approved Use Danazol is indicated for the treatment of endometriosis amenable to hormonal management; for the treatment of fibrocystic Breast Disease and for the prevention of attacks of angioedema of all types (cutaneous, abdominal, laryngeal) in males and females. Launch Date 1996
Fibrocystic breast disease 1 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f2c9b713-aafc-49ca-866e-334d9b5c2e2d	Palliative	Approved 8429	DANAZOL Approved Use Danazol is indicated for the treatment of endometriosis amenable to hormonal management; for the treatment of fibrocystic Breast Disease and for the prevention of attacks of angioedema of all types (cutaneous, abdominal, laryngeal) in males and females. Launch Date 1996
Hereditary angioedema 3 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f2c9b713-aafc-49ca-866e-334d9b5c2e2d	Preventing	Approved 8429	DANAZOL Approved Use Danazol is indicated for the treatment of endometriosis amenable to hormonal management; for the treatment of fibrocystic Breast Disease and for the prevention of attacks of angioedema of all types (cutaneous, abdominal, laryngeal) in males and females. Launch Date 1996

C_max

Value	Dose	Co-administered	Analyte	Population
69.6 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017557s033s039s040s041s042lbl.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		DANAZOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
601 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017557s033s039s040s041s042lbl.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		DANAZOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
9.7 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017557s033s039s040s041s042lbl.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		DANAZOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	inhibitor 1767	inhibitor 1852 substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2J2 16 CYP1A2 1524 CYP2C19 1478 CYP3A 214	CYP2J2 56 CYP2C8 693 CYP2C19 991 CYP1A2 1054 CYP1A1 349 CYP2A6 543 CYP2B6 664 FMO 35

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26048912/	no
CYP2J2 19	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26048912/	yes [IC50 0.05 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26048912/	yes
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26048912/	yes
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26048912/	yes
CYP3A 298	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26048912/	yes

Drug as victim

Target	Modality	Activity
CYP1A1 349	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/19923256/	no
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/19923256/	no
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/19923256/	no
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/19923256/	no
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/19923256/	no
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/19923256/	no
FMO 35	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/19923256/	no
CYP2J2 56	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/19923256/	yes [Km 2.15 uM]
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/19923256/	yes [Km 3.62 uM]
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/19923256/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4315	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4315
ChemicalBook	CB9463336	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9463336
ZINC	ZINC000003881958	http://zinc15.docking.org/substances/ZINC000003881958
eMolecules	2726153	https://www.emolecules.com/cgi-bin/more?vid=2726153
eMolecules	30512482	https://www.emolecules.com/cgi-bin/more?vid=30512482

PubMed

Title	Date	PubMed
A report on alterations to the speaking and singing voices of four women following hormonal therapy with virilizing agents.	1999 Dec	10622516
Hepatocellular adenomas in patients taking danazol for hereditary angio-oedema.	1999 Mar 27	10199359
[Methimazole-induced aplastic anemia].	1999 Sep	10544668
Danazol for pelvic pain associated with endometriosis.	2001	11687066
GC-MS characterization of urinary metabolites and changes of ethisterone and testosterone profile after oral administration of danazol in equine.	2001 Apr	11442791
The possible anti-inflammatory role of circulating human leukocyte antigen levels in women with endometriosis after treatment with danazol and leuprorelin acetate depot.	2001 Apr	11405553
Sensory perineuritis presented as a mononeuritis multiplex associated with livedo vasculitis.	2001 Apr	11311480
[The chronic Philadelphia chromosome-negative myeloproliferative syndrome II. Clinical findings, diagnostics and treatment].	2001 Apr 30	11379260
Long-term follow-up of a controlled trial of laser laparoscopy for pelvic pain.	2001 Apr-Jun	11394422
Therapies for the treatment of abnormal uterine bleeding.	2001 Dec	12112970
Danazol and limb-threatening arterial thrombosis: two case reports.	2001 Dec	11743571
Influence of drug treatment on survival of dogs with immune-mediated hemolytic anemia: 88 cases (1989-1999).	2001 Feb 15	11229506
[Combined treatment of endometriosis--medication and surgery].	2001 Jan	11235157
[Local administration of danazol on pelvic endometriosis and uterine adenomyosis].	2001 Jan	11235155
[Low-dose danazol therapy in endometriosis].	2001 Jan	11235154
[Danazol--up-to-date aspect for endometriosis].	2001 Jan	11235153
Hygroscopicity, phase solubility and dissolution of various substituted sulfobutylether beta-cyclodextrins (SBE) and danazol-SBE inclusion complexes.	2001 Jan 16	11165075
The success of laser laparoscopy in the treatment of endometriosis: a two-step analysis.	2001 Jan-Mar	11303991
Medical and surgical therapies for pain associated with endometriosis.	2001 Mar	11268298
[Endometriosis of the abdominal wall: diagnosis and treatment techniques].	2001 May	11526776
[Pneumothorax during menstruation: a case report].	2001 May	11526763
[The evaluation of the effect of combined treatment (laparoscopic ante-fixation of the uterus and Danazol-therapy) in patients with endometriosis and retroflexion of the uterus].	2001 May	11526760
[Danazol-induced hepatitis with functional deficit of the C1 inhibitor].	2001 Nov	11862774
[The effectiveness of cyclosporin A in the treatment of autoimmune hemolytic anemia and Evans syndrome].	2001 Nov	11855146
Fatal acute hepatic failure induced by danazol in a patient with endometriosis and aplastic anemia.	2001 Nov	11757752
Impairment of CYP3A4 capacity in patients receiving danazol therapy: examination on oxidative cortisol metabolism.	2001 Oct	11607885
Danazol therapy in factor X deficiency.	2001 Sep	11554940
[Dysmenorrhea].	2001 Sep	11554049
Clarifying questionable dosages.	2001 Sep 1	11556662
Histomorphometric analysis: comparative study of manual and digital image analysis using reproductive organ as a model.	2002	12085619
Danazol for heavy menstrual bleeding.	2002	12076401
Remission of transformed myelodysplastic syndrome with fibrosis after danazol therapy.	2002 Apr	12071939
Risk factors for evolution of acquired aplastic anemia into myelodysplastic syndrome and acute myeloid leukemia after immunosuppressive therapy in children.	2002 Aug 1	12130487
Development and in vivo evaluation of buccal tablets prepared using danazol-sulfobutylether 7 beta-cyclodextrin (SBE 7) complexes.	2002 Jul	12115827
Pulsed high-dose dexamethasone therapy in children with chronic idiopathic thrombocytopenic purpura.	2002 Jul-Aug	12078864
Successful treatment of anemia in idiopathic myelofibrosis with recombinant human erythropoietin.	2002 Jun	12111781
Splenectomy for immune thrombocytopenic purpura: long-term results and treatment of postsplenectomy relapses.	2002 Jun	12107560
Inhibition of progesterone secretion with trilostane for mid-trimester termination of pregnancy: randomized controlled trials.	2002 Jun	12042266
A randomized trial of danazol pretreatment prior to endometrial resection.	2002 Jun 10	12039468
[Ureteral endometriosis: urological features].	2002 Mar	12053448
Conventional medical therapies for endometriosis.	2002 Mar	11949960
[Acquired angioneurotic edema. Apropos of a case].	2002 Mar	11928387
HIV-related thrombocytopenia.	2002 Mar	11914001
The influence of hormones and pharmaceutical agents on DHEA and DHEA-S concentrations: a review of clinical studies.	2002 Mar	11865961
Danazol linked to ovarian cancer.	2002 May	12067790
Autoimmune acquired form of angioedema that responded to danazol therapy.	2002 May	12058892
Angioedema and acquired C1 esterase inhibitor deficiency.	2002 May	12058878

Patents

Sample Use Guides

In Vivo Use Guide

Endometriosis: In moderate to severe disease, a starting dose of 800 mg given in two divided doses is recommended. For mild cases, an initial daily dose of 200 mg to 400 mg given in two divided doses is recommended. Fibrocystic Breast Disease: The total daily dosage of danazol for fibrocystic breast disease ranges from 100 mg to 400 mg given in two divided doses depending upon patient response. Hereditary Angioedema: It is recommended that the patient be started on 200 mg, two or three times a day.

Route of Administration: Oral

In Vitro Use Guide

Undissolved danazol significantly inhibited endometrial cell growth even at less than 100 ng/ml. At 500 ng/ml of fully dissolved danazol, which is the therapeutic dose, danazol solution inhibited leukemic cell growth but not endometrial cell growth.

Name

Type

Language

DANAZOL

Official Name

English

NSC-270916

Code

English

DANAZOL [USP-RS]

Common Name

English

17.ALPHA.-PREGNA-2,4-DIEN-20-YNO(2,3)-DISOXAZOL-17-OL

Common Name

English

Danazol [WHO-DD]

Common Name

English

DANAZOL [VANDF]

Common Name

English

DANAZOL [USAN]

Common Name

English

DANAZOL [MART.]

Common Name

English

DANAZOL [ORANGE BOOK]

Common Name

English

DANOCRINE

Brand Name

English

DANAZOL [JAN]

Common Name

English

DANAZOL [USP MONOGRAPH]

Common Name

English

danazol [INN]

Common Name

English

DANAZOL [MI]

Common Name

English

PREGNA-2,4-DIEN-20-YNO(2,3-D)ISOXAZOL-17-OL,(17.ALPHA.)-

Common Name

English

WIN-17757

Code

English

WIN 17,757

Code

English

Classification Tree Code System Code

NDF-RT

N0000008241