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 2637

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 8307	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 8.395488E11
Fibrocystic breast disease 1 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f2c9b713-aafc-49ca-866e-334d9b5c2e2d	Palliative	Approved 8307	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 8.395488E11
Hereditary angioedema 3 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f2c9b713-aafc-49ca-866e-334d9b5c2e2d	Preventing	Approved 8307	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 8.395488E11

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 1670	inhibitor 1695	inhibitor 1789 substrate 1168

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2J2 16 CYP1A2 1463 CYP2C19 1410 CYP3A 208	CYP2J2 54 CYP2C8 670 CYP2C19 955 CYP1A2 1013 CYP1A1 344 CYP2A6 510 CYP2B6 648 FMO 35

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1826	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/26048912/	no
CYP2J2 19	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/26048912/	yes [IC50 0.05 uM]
CYP1A2 1620	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/26048912/	yes
CYP2C19 1484	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/26048912/	yes
CYP2C9 1747	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/26048912/	yes
CYP3A 291	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/26048912/	yes

Drug as victim

Target	Modality	Activity
CYP1A1 344	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/19923256/	no
CYP1A2 1013	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/19923256/	no
CYP2A6 510	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/19923256/	no
CYP2B6 648	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/19923256/	no
CYP2C19 955	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/19923256/	no
CYP2C8 670	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/19923256/	no
FMO 35	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/19923256/	no
CYP2J2 54	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/19923256/	yes [Km 2.15 uM]
CYP3A4 1670	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/19923256/	yes [Km 3.62 uM]
CYP2D6 1168	substrate 3264 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
[Methimazole-induced aplastic anemia].	1999 Sep	10544668
[Spontaneous splenic rupture caused by spleen peliosis in a patient with autoimmune thrombocytopenic purpura treated with danazol].	2000 May 20	10919136
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
The treatment of endometriosis.	2001 Apr	11332005
Sensory perineuritis presented as a mononeuritis multiplex associated with livedo vasculitis.	2001 Apr	11311480
Solvent and solid-phase extraction of natural and synthetic anabolic steroids in human urine.	2001 Apr 25	11339285
Long-term follow-up of a controlled trial of laser laparoscopy for pelvic pain.	2001 Apr-Jun	11394422
Comparative effect of danazol and a GnRH agonist on monocyte chemotactic protein-1 expression by endometriotic cells.	2001 Feb	11216879
Influence of drug treatment on survival of dogs with immune-mediated hemolytic anemia: 88 cases (1989-1999).	2001 Feb 15	11229506
[Pathological findings of endometriosis].	2001 Jan	11235174
[Endometriosis of the urinary tract].	2001 Jan	11235166
[Thoracic endometriosis].	2001 Jan	11235165
[Gastrointestinal endometriosis].	2001 Jan	11235164
[Recto-vaginal endometriosis].	2001 Jan	11235163
[Strategy of treatment for infertile women with endometriosis].	2001 Jan	11235159
[Treatment for endometriosis with pain].	2001 Jan	11235158
[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
[Medical treatment of endometriosis: general approach].	2001 Jan	11235147
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
Effectiveness of postoperative adjuvant therapy in improving reproductive outcome of endometriosis-associated infertility.	2001 Jul	11579612
Role of splenectomy in the treatment of myelodysplastic syndromes with peripheral thrombocytopenia: a report on six cases.	2001 Jun	11417482
[Two case reports of long-term treatment of endometriosis with cyproterone acetate].	2001 Mar	11340959
Pulmonary nocardiosis associated with idiopathic thrombocytopenic purpura.	2001 Mar	11310493
Medical and surgical therapies for pain associated with endometriosis.	2001 Mar	11268298
Postcoital contraception.	2001 Mar	11219237
Long-term outcomes after treatment for refractory immune thrombocytopenic purpura.	2001 May 3	11336065
Treatment of autoimmune hemolytic anemias.	2001 Nov	11604584
Eradication of Helicobacter pylori and improvement of hereditary angioneurotic oedema.	2001 Nov 17	11728547
Benign breast disease.	2001 Sep	11594256
[Postcoital emergency contraception].	2001 Sep	11594152
Danazol therapy in factor X deficiency.	2001 Sep	11554940
[Dysmenorrhea].	2001 Sep	11554049
Clarifying questionable dosages.	2001 Sep 1	11556662
Danazol for heavy menstrual bleeding.	2002	12076401
Danazol therapy for thrombocytopenia in patients with myelodysplastic syndromes.	2002	12053153
Nonsteroidal anti-inflammatory drugs for heavy menstrual bleeding.	2002	11869575
Remission of transformed myelodysplastic syndrome with fibrosis after danazol therapy.	2002 Apr	12071939
Danazol therapy in factor X deficiency: more questions than answers.	2002 Jan	11886468
Hormonal emergency contraception.	2002 Jan	11794429
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
[Ureteral endometriosis: urological features].	2002 Mar	12053448
The influence of hormones and pharmaceutical agents on DHEA and DHEA-S concentrations: a review of clinical studies.	2002 Mar	11865961
Optimized conditions for MDCK permeability and turbidimetric solubility studies using compounds representative of BCS classes I-IV.	2002 May	11988394
Benign breast pain in women: a practical approach to evaluation and treatment.	2002 Spring	11991427

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