product name Mifepristone
Description: Mifepristone (also known as RU486, C-1073) is a synthetic steroid compound that is a highly active antagonist of progesterone receptor and glucocorticoid receptor with IC50 of 0.2 nM and 2.6 nM, respectively. Mifepristone is used as used as an abortifacient in the first two months of pregnancy, and in smaller doses as an emergency contraceptive. As a contraceptive agent, Mifepristone has been reported to reduce the size of uterine fibroids, and inhibit the growth of meningioma cells in vitro, in experimental animal models and in patients with inoperable meningiomas.
References: Bioorg Med Chem. 2006 Oct 1;14(19):6726-32; Clin Cancer Res. 2007 Jun 1;13(11):3370-9.
429.59
Formula
C29H35NO2
CAS No.
84371-65-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 85 mg/mL (197.9 mM)
Water: <1 mg/mL
Ethanol: 19 mg/mL (44.2 mM)
Solubility (In vivo)
Synonyms
RU486, C-1073
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19417523
| In Vitro |
In vitro activity: Mifepristone inhibit corticoid-induced transcription from a glucocorticoid response element (GRE)-linked luciferase reporter gene in the human lung carcinoma cell line A549. Moreover, Mifepristone also blocks progesterone induction of alkaline phosphatase activity in the human breast cancer cell line T47D. Mifepristone inhibits ovarian cancer cell growth of SK-OV-3 and OV2008 with IC50 of 6.25 μM and 6.91 μM, respectively. A recent study shows that Mifepristone induces caspase-1 over expression both in differentiated and undifferentiated caspase-1-embryonic stem cells. Kinase Assay: T47D alkaline phosphatase assay: T47D human breast cancer cells are plated in 96-well tissue culture plates at 104 cells per well in assay medium [RPMI medium without phenol red containing 5% (v/v) charcoal-treated FBS and 1% (v/v) penicillin–streptomycin]. Two days later, the medium is decanted and Mifepristone or control is added at a final concentration of 0.1% (v/v) dimethylsulfoxide in fresh assay medium. Twenty-four hours later, an alkaline phosphatase assay is performed using a SEAP kit. The medium is decanted and the cells are fixed for 30 minutes at room temperature with 5% (v/v) formalin. The cells are washed once at room temperature with Hanks buffered saline solution. Equal volumes (0.05 mL) of dilution buffer, assay buffer, and 1:20 substrate/enhancer mixture are then added. After 1-hour incubation in the dark at room temperature, the lysate is transferred to a white 96-well plate and luminescence is read using a LuminoSkan Ascen. A549 reporter assay: A549 human lung carcinoma cells are washed with OPTI-MEM I. The medium is removed and lipid–DNA complex solution (1.5 μg/mL of GRE-luciferase reporter DNA in 8.5 mL OPTI-MEM I plus 6 μL/mL DMRIE-C reagent in 8.5 mL OPTI-MEM I, combined, mixed and incubated at room temperature for 40 minutes) is overlayed onto the cells in a T160 flask. The cells are incubated for 16 hours at 37 °C in a CO2 incubator. The DNA-containing medium is removed and 30 mL of growth medium containing 5% (v/v) charcoal-treated fetal bovine serum is added. After 5-6 hours, the cells are seeded in 96-well plates and incubated overnight at 37 °C. Mifepristone is then added to each well followed by dexamethasone as a corticoid challenge. The cells are incubated for 24 hours. Luciferase assay buffer is added to each well and the cells are incubated for 30 minutes at room temperature. Luciferase activity is measured in a DYNEX Microlite plate on a TopCount. Cell Assay: Cell growth is evaluated in various ovarian cancer cell lines (OV2008 and SK-OV-3 cells) that are subjected to dose-response or time course treatments. Media containing each of the doses of fresh steroids is replaced every 24 hours. Control groups of cells are treated with vehicle ethanol at a final concentration of less than 0.05%. Number of viable cells is evaluated by trypsinization and counting in a hemocytometer chamber using trypan blue dye exclusion. Experiments are conducted in media without phenol red and supplemented with charcoal extracted fetal bovine serum, or media containing unextracted serum and having phenol red. Similar results are obtained with both media preparations; therefore, after performing the growth curves, all subsequent experiments are conducted using media with unextracted serum and in the presence of phenol red. When indicated, the proliferation IC50s are calculated using software designed to study drug interaction. |
|---|---|
| In Vivo | Mifepristone can impair the growth of SK-OV-3 tumors in immunosuppressed mice at 0.5 mg/day and 1 mg/day. Mifepristone inhibits the prostate weight significantly in the highest doses in vivo, and inhibits growth of the prostate gland produced by dihydrotestosterone (DHT) to a greater extent than the induction of atrophy and cell death in rats. |
| Animal model | SK-OV-3 ovarian cancer cells are injected into immunosuppressed mice. |
| Formulation & Dosage | Formulated in Constant release pellets; 0.5 or 1 mg/day; Implanted s.c. with pellets |
| References | Bioorg Med Chem. 2006 Oct 1;14(19):6726-32; Clin Cancer Res. 2007 Jun 1;13(11):3370-9. |
