The primary targets of Danazol include the androgen receptor (AR) and the anterior pituitary gland. Danazol is a weak androgen and anterior pituitary suppressant. It suppresses the production of gonadotrophins by inhibiting the pituitary output of gonadotropins. The compound has antigonadotropic and anti-estrogenic activities. Danazol also has potential to cause PKC translocation in breast cancer cells. The compound's effects on the hypothalamic-pituitary-gonadal axis underlie its clinical uses in endometriosis and other hormone-dependent conditions. The androgen receptor binding activity contributes to its weak androgenic effects.

In vitro, Danazol has been shown to have potential to cause PKC translocation, cell cycle dysregulation, and apoptosis in breast cancer cells. The compound's effects on breast cancer cells suggest potential antiproliferative activity. Danazol's antigonadotropic and anti-estrogenic activities can be evaluated in cell-based assays measuring hormone-responsive gene expression or cell proliferation. The compound's weak androgenic effects can be assessed using androgen receptor reporter assays. These in vitro studies demonstrate the compound's complex pharmacology involving both steroid receptor and non-receptor-mediated effects.

In vivo, Danazol has been used clinically for the treatment of endometriosis, fibrocystic breast disease, and hereditary angioedema. The compound's anterior pituitary suppressant activity reduces gonadotropin levels, leading to decreased ovarian steroid production and regression of endometriotic lesions. Danazol's weak androgenic effects contribute to its therapeutic effects in hereditary angioedema. The compound has been studied in animal models of endometriosis and other hormone-dependent conditions. Clinical studies have demonstrated efficacy in these indications. The compound is a synthetic steroid with established clinical use.

In vitro enzyme/receptor binding studies for Danazol focus on its interactions with steroid receptors and pituitary hormone regulation. Androgen receptor binding can be assessed using radioligand competition assays. Estrogen and progesterone receptor binding can also be evaluated. The compound's effects on gonadotropin secretion can be studied in pituitary cell cultures by measuring LH and FSH release. PKC translocation can be assessed by Western blot or immunofluorescence in breast cancer cells. These methods are for research purposes only. Standard assay conditions include appropriate buffer systems and controls.

In vitro cell-based assays for Danazol evaluate its effects on hormone-responsive cell lines. Breast cancer cell lines (e.g., MCF-7, T47D) are treated with Danazol at various concentrations (typically 0.1-100 µM) for 24-72 hours. Cell proliferation is assessed using MTT or BrdU incorporation assays. Cell cycle analysis is performed using propidium iodide staining and flow cytometry. Apoptosis is measured using Annexin V/PI staining or caspase activity assays. PKC translocation is assessed by Western blot or immunofluorescence. Hormone-responsive gene expression is measured by qRT-PCR. Standard cell culture conditions are used.

In vivo animal studies for Danazol utilize models of endometriosis, breast cancer, or other hormone-dependent conditions. Endometriosis models in rats or mice involve surgical induction of endometriotic lesions followed by Danazol treatment. Breast cancer xenograft models are used to evaluate antitumor effects. Danazol is administered via oral or intraperitoneal routes at various doses. Endometriotic lesion size, tumor growth, hormone levels, and histology are assessed. All procedures must comply with institutional animal care guidelines. The compound has established clinical use in these indications.

Metabolism / Metabolites
Metabolized in the liver, the main metabolites are norethindrone and 17-hydroxymethylnorethindrone.

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Biological half-life
Approximately 24 hours.

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The pharmacokinetic properties of Danazol have been characterized in clinical studies. The compound is orally bioavailable and is absorbed following oral administration. Danazol has a molecular weight of 337.46 g/mol. The compound is metabolized in the liver and excreted in urine and feces. The half-life is approximately 4-5 hours. Danazol binds extensively to plasma proteins (primarily sex hormone-binding globulin and albumin). The compound's pharmacokinetic profile supports oral dosing for clinical use.

The toxicity profile of Danazol has been characterized in clinical use. Common adverse effects include weight gain, fluid retention, acne, hirsutism, voice deepening, and other androgenic effects. Hepatotoxicity is a serious but rare adverse effect. Danazol can also cause changes in lipid profiles and may increase the risk of cardiovascular events. The compound is contraindicated during pregnancy due to potential teratogenic effects. The compound is for research use only and is not approved for clinical use in research settings. Standard safety precautions for handling pharmaceutical compounds apply.

Danazol may cause developmental toxicity depending on state or federal labeling requirements. Danazol is a 17β-hydroxysteroid and a terminal alkyne compound. It has anti-estrogenic, estrogen antagonist, and anti-aging effects. It is derived from the hydrogenation of pregnane. It is a synthetic steroid with anti-gonadotropic and anti-estrogenic activity, acting as an anterior pituitary inhibitor by inhibiting the output of pituitary gonadotropins. It has some androgenic properties. Danazol has been used to treat endometriosis and some benign breast diseases. Danazol is an androgen. The mechanism of action of danazol is as an androgen receptor agonist. Danazol is a synthetic androgen derived from ethinyltestosterone. Danazol indirectly reduces estrogen production by decreasing the secretion of follicle-stimulating hormone and luteinizing hormone from the pituitary gland, and exerts anti-estrogenic, anabolic, and weak androgenic effects by binding to sex hormone receptors in target tissues. (NCI04)
A synthetic steroid with anti-gonadotropic and anti-estrogen activity, acting as an anterior pituitary inhibitor by suppressing the output of pituitary gonadotropins. It has some androgenic properties. Danazol has been used to treat endometriosis and some benign breast diseases.

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Drug Indications
Used to treat endometriosis and fibrocystic breast disease (in patients unresponsive to simple treatments). Also used to prevent various types of hereditary angioedema in men and women.

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Mechanism of Action
As a gonadotropin inhibitor, danazol may suppress the pituitary-ovarian axis by inhibiting the secretion of pituitary gonadotropins. Danazol can also suppress the pre-ovulatory surge of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), thereby reducing ovarian estrogen production. Danazol may also directly inhibit ovarian steroid production; bind to androgen, progesterone, and glucocorticoid receptors; bind to sex hormone-binding globulin and corticosteroid-binding globulin; and increase the metabolic clearance of progesterone. Another mechanism by which danazol promotes the regression of endometriosis may be by reducing the concentrations of IgG, IgM, and IgA, as well as the levels of phospholipids and IgG isotope autoantibodies. In the treatment of endometriosis, due to the suppression of ovarian function, danazol causes both normal and ectopic endometrial tissue to lose activity and atrophy, leading to anovulation and amenorrhea. In fibrocystic breast disease, the exact mechanism of action of danazol is unclear, but it may be related to the suppression of estrogen stimulation caused by decreased ovarian estrogen secretion. Danazol may also act directly on steroid receptor sites in breast tissue, leading to nodule disappearance, relief of pain and tenderness, and possible alteration of the menstrual cycle. In the case of hereditary angioedema, danazol corrects the underlying biochemical deficiency by increasing the serum concentration of the deficient C1 esterase inhibitor, thereby increasing the serum concentration of the C4 component of the complement system. (Source: PharmGKB) Danazol is a derivative of the synthetic steroid norethindrone (a modified testosterone). It was initially approved by the U.S. Food and Drug Administration (FDA) as the first drug specifically for the treatment of endometriosis, but its role in endometriosis treatment has been superseded by gonadotropin-releasing hormone (GnRH) agonists. Danazol possesses anti-gonadotropic and anti-estrogenic activities. Danazol acts as an anterior pituitary inhibitor by inhibiting the output of pituitary gonadotropins. It also exhibits some androgenic properties.

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Additional information: Danazol has the CAS number 17230-88-5 and the molecular formula C₂₂H₂₇NO₂. The compound is a synthetic steroid derivative of ethisterone. Danazol suppresses the production of gonadotrophins and has weak androgenic effects. The compound acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. Danazol has antigonadotropic and anti-estrogenic activities. The compound has been used clinically for endometriosis, fibrocystic breast disease, and hereditary angioedema. Danazol was developed by Sanofi Aventis. This product is for research use only and is not approved for clinical or therapeutic applications in research settings.

C22H27NO2

337.46

337.204

C, 78.30; H, 8.06; N, 4.15; O, 9.48

17230-88-5

17230-88-5

28417

White to light yellow crystalline powder

1.2±0.1 g/cm3

478.2±45.0 °C at 760 mmHg

224.4-226.8ºC

243.0±28.7 °C

0.0±1.3 mmHg at 25°C

1.604

4.7

1

3

1

25

677

6

C#C[C@]1(O)CC[C@@]2([H])[C@]3([H])CCC4=CC5=C(C=NO5)C[C@]4(C)[C@@]3([H])CC[C@@]21C

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

(1S,2R,13R,14S,17R,18S)-17-ethynyl-2,18-dimethyl-7-oxa-6-azapentacyclo[11.7.0.02,10.04,8.014,18]icosa-4(8),5,9-trien-17-ol

Danazol; Danol; Danocrine; Chronogyn; Ladogal; Cyclomen

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~25 mg/mL (~74.1 mM;)
Ethanol: ~20 mg/mL (~59.3 mM)

Solubility in Formulation 1: 2.5 mg/mL (7.41 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.41 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 3: ≥ 2 mg/mL (5.93 mM) (saturation unknown) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear EtOH stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 4: ≥ 2 mg/mL (5.93 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix well.

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 (Please use freshly prepared in vivo formulations for optimal results.)