美服培酮作用机制 - Medchemexpress - MCE中国

1、Product Data SheetMifepristoneCat. No.: HY-13683CAS No.: 84371-65-3分式: CHNO分量: 429.59作靶点: Progesterone Receptor; Glucocorticoid Receptor; Autophagy作通路: Others; GPCR/G Protein; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 59 mg/mL (137.34 mM)* means

2、soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 2.3278 mL 11.6390 mL 23.2780 mL5 mM 0.4656 mL 2.3278 mL 4.6556 mL10 mM 0.2328 mL 1.1639 mL 2.3278 mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储

3、存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.82 mM); Clear solution此案可获得 2.5

4、 mg/mL (5.82 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.82 mM); Clear solutionPage 1 of 2 www.MedChemE此案可获得 2.5 mg/mL (5.82 mM，饱和度未知) 的澄清溶液。

5、以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合均匀。3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.82 mM); Clear solution此案可获得 2.5 mg/mL (5.82 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Mife

6、pristone体酮受体 (PR) 和糖质激素受体 (GR) 拮抗剂，体外实验中的 IC50 值分别为0.2 nM 和2.6 nM。IC & Target IC50: 0.2 nM (progesterone receptor, in T47D cells), 2.6 nM (glucocorticoid receptor, in A549 cells)1体外研究 The discovery of the first competitive progesterone antagonist, Mifepristone, has stimulated an intense search formo

7、re potent and more selective antiprogestins1. Cell growth is evaluated after 4 days of exposure to Mifepristone at10 M, a concentration close to the plasma concentration achievable in humans. The antiproliferative effect ofCisplatin is potentiated when administered in combination with Mifepristone i

8、n HeLa cells. The IC50 of Cisplatin incombination with Mifepristone is lower (14.2 M) than that of Cisplatin alone (34.2 M) in HeLa cells with anapproximately 2.5-fold difference. After treatment with Mifepristone, the accumulation of intracellular Cisplatin inHeLa cells is 2-fold greater, represent

9、ing a significant difference (p=0.009), compare with Cisplatin alone from 0.79 to1.52 g/mg of protein2.体内研究 The cervix tumor xenograft models are treated with Cisplatin alone, there is a tumor growth inhibition compare withcontrol group. However, the tumor weight loss is even more significant (p0.05

10、) with the combination of Cisplatinand Mifepristone at the doses used, showing a decrease of 50% compared with the treatments alone by the end ofthe study2. Adult male Sprague-Dawley rats are subjected to a 4-day binge-like EtOH administration regimen (3 to 5g/kg/i.g. every 8 hours designed to produ

11、ce peak blood EtOH levels (BELs) of 300 mg/dL). Subgroups of animalsreceive s.c. injection of Mifepristone (20 or 40 mg/kg in peanut oil). Although Mifepristone produces no significantchanges in behavior of EtOH-nave animals, pretreatment with Mifepristone (40 mg/kg) significantly reducestheseverity

12、 of EtOH withdrawal. Asignificant interaction between diet and drug, F(5,55)=3.92, p0.05, such that EtOH-treated animals receiving vehicle or 20 mg/kg of Mifepristone displayssignificantly more signs of EtOH withdrawalthan does EtOH-nave animals receiving the same drug treatment. Importantly, treatm

13、ent with 40 mg/kg ofMifepristone significantly reduces the severity of EtOH withdrawal, in a dose-dependent manner3.PROTOCOLKinase Assay 1 T47D human breast cancer cells are plated in 96-well tissue culture plates at 10,000 cells per well in assay mediumRPMI medium without phenol red containing 5% (

14、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 usinga SEAP ki

15、t. Briefly, the medium is decanted and the cells are fixed for 30 min at room temperature with 5% (v/v)formalin. The cells are washed once at room temperature with Hanks buffered saline solution. Equal volumes (0.05mL) of 1 dilution buffer, assay buffer, and 1:20 substrate/enhancer mixture are then

16、added. After a 1-h incubation atroom temperature in the dark, the lysate is transferred to a white 96-well plate and luminescence is read using aLuminoSkan Ascent1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Page 2 of 3 www.MedChemECell Assay 2 The

17、HeLa and CaSki human cervical cancer cell lines are used. The effect of Mifepristone on proliferation of cellsexposed to Cisplatin is evaluated using the XTT assay. The assay is based on the cleavage of the yellow tetrazoliumsalt XTT to form an orange formazan dye by metabolically active cells. The

18、procedure is as follows. Cells are seededinto 96-well plates; Costar at a density of 6103 viable cells per well in 100 L culture medium. At the end oftreatment with Cisplatin alone or the combination of Cisplatin plus Mifepristone, 50 L XTT is added to each well(final concentration 0.3 mg/mL), follo

19、w by incubation for 4 h in a humidified atmosphere containing 5% CO2 at 37C.The absorbance of the samples is measured spectrophotometrically at 492 nm using a microtiter plate ELISA reader2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice2Adm

20、inistration 23 Female Nude mice between 6-8 weeks of age are implanted subcutaneously with 6106 HeLa cells in a flank. Oncetumors are 55 mm, the animals are pair-matched into treatment and control groups. Each group consist of 8tumor-bearing mice. The intraperitoneal administration of drugs or vehic

21、le begin on day 0. Cisplatin, as a singleagent, is administered intraperitoneally at a dose of 3 mg/kg daily on days 1 through 3; the dose of Mifepristone, as asingle agent, is 2 mg/kg/day subcutaneously for 3 days; in the combination study, the mice concurrently receiveCisplatin on the same schedul

22、e, and Mifepristone at the same dose 3 days previous to the administration of Cisplatin.The control animals receive only the vehicle. After administration of the drugs, mice are weighed and the tumors aremeasured with a caliper twice weekly. The tumor weight is calculated. Experiment is conducted fo

23、r 74 days, afterwhich time all animals are weighed and humanely euthanized.Rats3Adult male Sprague-Dawley rats, weighing between 224 and 245 g upon arrival, are used. Mifepristone (20 or 40mg/kg) or vehicle (peanut oil) are administered subcutaneously (s.c.) once daily following the 0800 administrat

24、ion ofEtOH or control diet. Mifepristone is suspended in peanut oil and sonicated for 30 minutes at least 24 hours prior toinjection, it is then stored at 4C until needed. Suspension is vortexed for 10 to 15 minutes prior to and as neededthroughout dosing.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Sci Transl Med. 2020 May 6;12(542). pii: eaba0769. Arch Toxicol. 2020 Jun 3. Am J Physiol Cell Physiol. 2019 Sep 11. Sci Rep. 2017 Jul 26;7(1):6