美服培酮作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetMifepristoneCat. No.: HY-13683CAS No.: 84371-65-3分式: CHNO分量: 429.59作靶點(diǎn): Progesterone Receptor; Glucocorticoid Receptor; Autophagy作通路: Others; GPCR/G Protein; Autophagy儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 59 mg/mL (137.34 mM)* means

2、soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液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請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)

3、存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.82 mM); Clear solution此案可獲得 2.5

4、 mg/mL (5.82 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.82 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (5.82 mM，飽和度未知) 的澄清溶液。

5、以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.82 mM); Clear solution此案可獲得 2.5 mg/mL (5.82 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Mife

6、pristone體酮受體 (PR) 和糖質(zhì)激素受體 (GR) 拮抗劑，體外實(shí)驗(yàn)中的 IC50 值分別為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體外研究 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.體內(nèi)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.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) 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