Synonym
Danazol; Danocrine; Danol; Cyclomen; Chronogyn; Ladogal
IUPAC/Chemical Name
(1R,3aS,3bR,10aR,10bS,12aS)-1-ethynyl-10a,12a-dimethyl-2,3,3a,3b,4,5,10,10a,10b,11,12,12a-dodecahydro-1H-cyclopenta[7,8]phenanthro[3,2-d]isoxazol-1-ol
InChi Key
POZRVZJJTULAOH-LHZXLZLDSA-N
InChi Code
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
SMILES Code
C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@]2(C#C)O)CCC4=CC5=C(C[C@]34C)C=NO5
Appearance
White to light yellow crystalline powder.
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Danazol is a derivative of the synthetic steroid ethisterone, that suppresses the production of gonadotrophins and has some weak androgenic effects.
In vitro activity:
In the present study, a clinically used synthetic steroid hormone, danazol, was investigated for its CS properties and cytotoxic mechanisms. Danazol exhibited strong and moderate selectivity toward HepG2/VIN (SI 211.83) and NCI-H460/MX20 (SI 4.45), demonstrating CS effects across multiple kinds of MDR cancer cell lines (Table 1). In the cell cycle distribution analysis, 40x higher concentration of danazol for 24 h was first treated to evaluate the acute selective-effect of danazol in MDR cell lines. The results showed that KB/VIN cells represented an increase in the subG1-phase after high-dose and short-term danazol treatment. Danazol significantly activated caspase-8 in the KB/VIN, but not the HeLaS33, cell line (Fig. 5a). Moreover, danazol elicited high ROS levels in HeLaS3 as well as KB/VIN cells (Fig. 5c). These results demonstrated the compound’s selective property and apoptosis regulation in MDR cancer cells. The effects of danazol were further investigated on STAT3-related pathways. The data showed that danazol significantly reduced the phosphorylation of STAT3 as well as downstream MYC expression in MDR KB/VIN cells but not the parental HeLaS3 cells (Fig. 6a,b). In addition, the ELISA results demonstrated that danazol treatment inhibited CDC25 and CDK1 activation in KB/VIN cells (Fig. 6c,d). Furthermore, danazol treatment also resulted in increased levels of p21 in KB/VIN cells (Fig. 6e). Taken together, the results suggest that danazol exerts a CS effect by inhibiting the STAT3 pathway in MDR cancer cells and thus provides a possible solution for MDR cancers.
Reference: Sci Rep. 2019 Aug 12;9(1):11628. https://pubmed.ncbi.nlm.nih.gov/31406162/
In vivo activity:
The aim of this study was to investigate the effect of danazol on alloimmune responses in murine heart transplantation. CBA male mice (H2(k) ) underwent transplantation of C57BL/6 male (H2(b) ) hearts and received a single dose of danazol (0.4, 1.2 or 4mg/kg/day) by intraperitoneal injection on the day of transplantation and for 6 days thereafter. The median survival time (MST) of allografts in danazol-treated (1.2 and 4mg/kg/day) mice was 28 and 63 days, respectively, compared with 7days in untreated mice. Moreover, secondary CBA recipients given whole splenocytes or CD4(+) cells from primary danazol-treated (4mg/kg/day) CBA recipients 30 days after transplantation had prolonged allograft survival (MSTs, 29 and 60days, respectively). Cell proliferation, interleukin (IL)-2 and interferon-γ were suppressed in danazol-treated mice, whereas IL-4 and IL-10 were up-regulated. Moreover, danazol directly suppressed allo-proliferation in a mixed leukocyte culture. Flow cytometry showed an increased CD4(+) CD25(+) Foxp3(+) cell population in splenocytes from danazol-treated mice. In conclusion, danazol prolongs cardiac allograft survival and generates regulatory CD4(+) cells.
Reference: Transpl Int. 2012 Mar;25(3):357-65. https://pubmed.ncbi.nlm.nih.gov/22239184/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
35.0 |
103.72 |
| Ethanol |
20.0 |
56.27 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
337.46
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Kusakabe K, Morishima S, Nakamuta N, Li ZL, Otsuki Y. Effect of danazol on NK cells and cytokines in the mouse uterus. J Reprod Dev. 2007 Feb;53(1):87-94. doi: 10.1262/jrd.18074. Epub 2006 Nov 1. PMID: 17077583. 2. Chang YT, Teng YN, Lin KI, Wang CCN, Morris-Natschke SL, Lee KH, Hung CC. Danazol mediates collateral sensitivity via STAT3/Myc related pathway in multidrug-resistant cancer cells. Sci Rep. 2019 Aug 12;9(1):11628. doi: 10.1038/s41598-019-481692. PMID: 31406162; PMCID: PMC6690972.
3. Uchiyama M, Jin X, Zhang Q, Hirai T, Bashuda H, Watanabe T, Amano A, Niimi M. Danazol induces prolonged survival of fully allogeneic cardiac grafts and maintains the generation of regulatory CD4(+) cells in mice. Transpl Int. 2012 Mar;25(3):357-65. doi: 10.1111/j.1432-2277.2011.01427.x. Epub 2012 Jan 13. PMID: 22239184.
In vitro protocol:
1. Kusakabe K, Morishima S, Nakamuta N, Li ZL, Otsuki Y. Effect of danazol on NK cells and cytokines in the mouse uterus. J Reprod Dev. 2007 Feb;53(1):87-94. doi: 10.1262/jrd.18074. Epub 2006 Nov 1. PMID: 17077583. 2. Chang YT, Teng YN, Lin KI, Wang CCN, Morris-Natschke SL, Lee KH, Hung CC. Danazol mediates collateral sensitivity via STAT3/Myc related pathway in multidrug-resistant cancer cells. Sci Rep. 2019 Aug 12;9(1):11628. doi: 10.1038/s41598-019-481692. PMID: 31406162; PMCID: PMC6690972.
In vivo protocol:
1. Kusakabe K, Morishima S, Nakamuta N, Li ZL, Otsuki Y. Effect of danazol on NK cells and cytokines in the mouse uterus. J Reprod Dev. 2007 Feb;53(1):87-94. doi: 10.1262/jrd.18074. Epub 2006 Nov 1. PMID: 17077583. 2. Uchiyama M, Jin X, Zhang Q, Hirai T, Bashuda H, Watanabe T, Amano A, Niimi M. Danazol induces prolonged survival of fully allogeneic cardiac grafts and maintains the generation of regulatory CD4(+) cells in mice. Transpl Int. 2012 Mar;25(3):357-65. doi: 10.1111/j.1432-2277.2011.01427.x. Epub 2012 Jan 13. PMID: 22239184.
1: Al-Badr AA. Danazol. Profiles Drug Subst Excip Relat Methodol. 2022;47:149-326. doi: 10.1016/bs.podrm.2021.10.005. Epub 2021 Dec 23. PMID: 35396014.
2: Madanes AE, Farber M. Danazol. Ann Intern Med. 1982 May;96(5):625-30. doi: 10.7326/0003-4819-96-5-625. PMID: 7041729.
3: Donaldson VH. Danazol. Am J Med. 1989 Sep;87(3N):49N-55N. PMID: 2486535.
4: Hughes E, Tiffin G, Vandekerckhove P. Danazol for unexplained infertilty. Cochrane Database Syst Rev. 2000;(2):CD000069. doi: 10.1002/14651858.CD000069. Update in: Cochrane Database Syst Rev. 2007;(1):CD000069. PMID: 10796484.
5: Hughes E, Brown J, Tiffin G, Vandekerckhove P. Danazol for unexplained subfertility. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD000069. doi: 10.1002/14651858.CD000069.pub2. PMID: 17253444.
6: Barbieri RL. Danazol. Ann Intern Med. 1982 Aug;97(2):286. doi: 10.7326/0003-4819-97-2-286_1. PMID: 7103299.
7: Barbieri RL, Ryan KJ. Danazol: endocrine pharmacology and therapeutic applications. Am J Obstet Gynecol. 1981 Oct 15;141(4):453-63. doi: 10.1016/0002-9378(81)90611-6. PMID: 7025640.
8: Beaumont H, Augood C, Duckitt K, Lethaby A. Danazol for heavy menstrual bleeding. Cochrane Database Syst Rev. 2007 Jul 18;2007(3):CD001017. doi: 10.1002/14651858.CD001017.pub2. PMID: 17636649; PMCID: PMC7028060.
9: Chalmers JA. Danazol in the treatment of endometriosis. Drugs. 1980 May;19(5):331-41. doi: 10.2165/00003495-198019050-00002. PMID: 6993180.
10: Danazol--good mainly for endometriosis. Drug Ther Bull. 1990 Mar 19;28(6):22-4. PMID: 2130010.
11: Shepherd J. Danazol and plasma lipoprotein metabolism. Int J Gynaecol Obstet. 1995 Sep;50 Suppl 1:S23-6. doi: 10.1016/0020-7292(95)02511-a. PMID: 8529771.
12: Selak V, Farquhar C, Prentice A, Singla A. Danazol for pelvic pain associated with endometriosis. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD000068. doi: 10.1002/14651858.CD000068.pub2. PMID: 17943735.
13: Selak V, Farquhar C, Prentice A, Singla A. Danazol for pelvic pain associated with endometriosis. Cochrane Database Syst Rev. 2001;(4):CD000068. doi: 10.1002/14651858.CD000068. Update in: Cochrane Database Syst Rev. 2007;(4):CD000068. PMID: 11687066.
14: Selak V, Farquhar C, Prentice A, Singla A. Danazol for pelvic pain associated with endometriosis. Cochrane Database Syst Rev. 2000;(2):CD000068. doi: 10.1002/14651858.CD000068. Update in: Cochrane Database Syst Rev. 2001;(4):CD000068. PMID: 10796483.
15: Greenblatt B, Ben-Nun I. Danazol in the treatment of mammary dysplasia. Drugs. 1980 May;19(5):349-55. doi: 10.2165/00003495-198019050-00004. PMID: 6993181.
16: Plano VF. Danazol: review of recent studies. J Am Osteopath Assoc. 1980 Apr;79(8):530-4. PMID: 6988373.
17: Beaumont H, Augood C, Duckitt K, Lethaby A. Danazol for heavy menstrual bleeding. Cochrane Database Syst Rev. 2002;(2):CD001017. doi: 10.1002/14651858.CD001017. Update in: Cochrane Database Syst Rev. 2007;(3):CD001017. PMID: 12076401.
18: Letchumanan P, Thumboo J. Danazol in the treatment of systemic lupus erythematosus: a qualitative systematic review. Semin Arthritis Rheum. 2011 Feb;40(4):298-306. doi: 10.1016/j.semarthrit.2010.03.005. Epub 2010 Jun 11. PMID: 20541792.
19: Daniel GR. Danazol activity. Cancer Chemother Pharmacol. 1981;6(1):101. doi: 10.1007/BF00253018. PMID: 7273264.
20: Dmowski WP. Danazol-induced pseudomenopause in the management of endometriosis. Clin Obstet Gynecol. 1988 Dec;31(4):829-39. doi: 10.1097/00003081-198812000-00009. PMID: 3067931.
