tcsc1435 Mifepristone

Mifepristone is a progesterone receptor (PR) antagonist (IC₅₀=0.2 nM) in a T47D cell-based assay, also is a glucocorticoid receptor (GR) antagonist (IC₅₀=2.6 nM) in an A549 cell-based assay.



IC50 & Target: IC50: 0.2 nM (progesterone receptor, in T47D cells), 2.6 nM (glucocorticoid receptor, in A549 cells)^[1]

In Vitro: The discovery of the first competitive progesterone antagonist, Mifepristone, has stimulated an intense search for more potent and more selective antiprogestins^[1]. Cell growth is evaluated after 4 days of exposure to Mifepristone at 10 μM, a concentration close to the plasma concentration achievable in humans. The antiproliferative effect of Cisplatin is potentiated when administered in combination with Mifepristone in HeLa cells. The IC₅₀ of Cisplatin in combination with Mifepristone is lower (14.2 μM) than that of Cisplatin alone (34.2 μM) in HeLa cells with an approximately 2.5-fold difference. After treatment with Mifepristone, the accumulation of intracellular Cisplatin in HeLa cells is 2-fold greater, representing a significant difference (p=0.009), compare with Cisplatin alone from 0.79 to 1.52 μg/mg of protein^[2].

In Vivo: The cervix tumor xenograft models are treated with Cisplatin alone, there is a tumor growth inhibition compare with control group. However, the tumor weight loss is even more significant (p<0.05) with the combination of Cisplatin and Mifepristone at the doses used, showing a decrease of ~50% compared with the treatments alone by the end of the study^[2]. Adult male Sprague-Dawley rats are subjected to a 4-day binge-like EtOH administration regimen (3 to 5 g/kg/i.g. every 8 hours designed to produce peak blood EtOH levels (BELs) of <300 mg/dL). Subgroups of animals receive s.c. injection of Mifepristone (20 or 40 mg/kg in peanut oil). Although Mifepristone produces no significant changes in behavior of EtOH-naïve animals, pretreatment with Mifepristone (40 mg/kg) significantly reducesthe severity of EtOH withdrawal. Asignificant interaction between diet and drug, F(5,55)=3.92, p<0.05, such that EtOH-treated animals receiving vehicle or 20 mg/kg of Mifepristone displayssignificantly more signs of EtOH withdrawal than does EtOH-naïve animals receiving the same drug treatment. Importantly, treatment with 40 mg/kg of Mifepristone significantly reduces the severity of EtOH withdrawal, in a dose-dependent manner^[3].