Everolimus-RAD001-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEEverolimusCat. No.: HY-10218CAS No.: 159351-69-6Synonyms: RAD001; SDZ-RAD分式: CHNO分量: 958.22作靶點: mTOR; FKBP; Autophagy作通路: PI3K/Akt/mTOR; Apoptosis; Autophagy;Immunology/Inflammation儲存式: Powder -20C 3 years4C 2 years* 該產(chǎn)品在溶液狀態(tài)不穩(wěn)定

2、，建議您現(xiàn)現(xiàn)配，即刻使。溶解性數(shù)據(jù)體外實驗 DMSO : 54 mg/mL (56.35 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (2.61 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (2.61 mM); Precipitated solution3. 請依序添加每種溶劑：

3、10% DMSO 90% corn oilSolubility: 2.5 mg/mL (2.61 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Everolimus (RAD001)有效的 mTOR 抑制劑，它與FKBP-12結(jié)合以產(chǎn)免疫抑制復合物。IC50 & Target mTOR5-6 nM (IC50)體外研究 Everolimus (RAD001) is an orally active derivative of rapamycin that inhibits the Ser/Thr kinase, mTOR 1. Inboth the sen

4、sitive murine B16/BL6 melanoma (IC50, 0.7 nM) and the insensitive human cervical KB-31(IC50, 1,778 nM), antiproliferative concentrations of Everolimus results in total dephosphorylation of S6K1and the substrate S6 and a shift in the mobility of 4E-BP1, which is indicative of a reduced phosphorylatio

5、nstatus 2. Everolimus exhibits a dose-dependent inhibition in both the total cells and the stem cells from theBT474 cell line and the primary breast cancer cells, albeit with different degrees of growth inhibition.Compare with the total cells, Everolimus is less effective in growth inhibition in the

6、 stem cells at all testedconcentrations (P50 values of Everolimus for BT474 and the primary CSCs are 2,054 and 3,227 nM, or 29times and 21 times greater than the IC50 values for their corresponding total cells, respectively 3.體內(nèi)研究 Everolimus is orally active in both mice and rats, producing an antit

7、umor effect that is characterized bydramatic reduction in tumor growth rates as opposed to producing tumor regressions. In the rat CA20498model, daily treatment with Everolimus (0.5 or 2.5 mg/kg) dose-dependently inhibits growth, and intermittentdosing using a higher dose of 5 mg/kg (once or twice p

8、er week) also shows similar antitumor efficacy.Inhibition by Everolimus is characterized by sustained suppression rather than regression and is notassociated with any body weight loss 1. The effect of Everolimus treatment (0.1-10 mg/kg/d) is selectiveand differ from the effects of PTK/ZK (100 mg/kg)

9、. With either growth factor, Everolimus dose-dependentlyincreases the hemoglobin content (convert to blood equivalents and indicative of the number of vessels aswell as vascular leakiness) but reduces the Tie-2 content (number of endothelial cells indicative of thenumber of vessels) and this is sign

10、ificant for VEGF stimulation but not bFGF stimulation. Thepharmacokinetics of Everolimus in mice shows that maximum levels of only 0.1 M are achieved in a humantumor xenograft following a single administration, whereas plasma levels reach 1 to 3 M for 4 h 2.PROTOCOLCell Assay 2 Tumor cells are plate

11、d into 96-well plates at densities ranging from 500 to 5,000/100 L/well, with repeatexperiments being done at an optimal cell number, typically 1,000 to 2,000 per well, and incubated overnight.Cells are exposed to Everolimus and incubated for 4 days and the cell number is determined by methyleneblue

12、 staining. For this, 50 L glutaraldehyde 20% (v/v) is added to the wells incubated for 10 min at roomtemperature. The culture medium is aspirated, cells are washed with distilled water, and 100 L methylene2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEblue 0.05% (w/v) in water is added and incubat

13、ed for 10 min at 37C. Stained cells are washed three timeswith water, 200 L HCl 3% (v/v) is added, and the plate shaken at room temperature for 20 min. Theabsorbance of each well is determined at 650 nm. The IC50 values are calculated using Softmax 2.0software 2.MCE has not independently confirmed t

14、he accuracy of these methods. They are for reference only.Animal Mice 2Administration 2 Everolimus, PTK/ZK, and their respective vehicles are prepared each day just before administration toanimals and the administration volume is individually adjusted based on animal body weight. In C57/BL6mice, Eve

15、rolimus is administered at doses ranging from 0.1 to 10 mg/kg/d orally (10 mL/kg) andpredominantly at 2.5 to 10 mg/kg because these doses provides the maximum effect. PTK/ZK isadministered at 50 to 100 mg/kg/d orally.Rats 2Wistar-Furth rats are divided into two equal groups based on body weight and

16、treated either with vehicle orEverolimus (10 mg/kg/d orally in mice and 5 mg/kg three times per week orally in rats). Directly after the firstmeasurement at baseline (day 0), Everolimus or vehicle is administered orally by gavage (10 mL/kg) for up to7 days maximum with subsequent magnetic resonance

17、measurements made within 30 min of the last dose.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 Nature. 2016 Dec 1;540(7631):119-123. Nat Med. 2016 Jul;22(7):723-6. Sci Transl Med. 2013 Jul 31;5(196):196ra99. J Clin Invest. 2017 Sep 1;127(9

18、):3339-3352. Cell Syst. 2018 Dec.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. OReilly T, et al. Biomarker Development for the Clinical Activity of the mTOR Inhibitor Everolimus (RAD001): Processes,Limitations, andFurther Proposals. Transl Oncol. 2010 Apr;3(2):65-79.2. Lane HA, et al. mTOR inhibitor RAD001 (everolimus) has antiangiogenic/vascular properties distinct from a VEGFR t