RTA-408-Omaveloxolone-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemERTA-408Cat. No.: HY-12212CAS No.: 1474034-05-3Synonyms: Omaveloxolone分式: CHFNO分量: 554.71作靶點(diǎn): Keap1-Nrf2作通路: NF-B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 : 100 mg/mL (180.27 mM)* means

2、soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 1.8027 mL 9.0137 mL 18.0274 mL5 mM 0.3605 mL 1.8027 mL 3.6055 mL10 mM 0.1803 mL 0.9014 mL 1.8027 mL請根據(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，并請注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn) 請根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍福渲魄罢埾扰渲瞥吻宓膬?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，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)

3、現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.51 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 RTA-408種抗氧化炎癥調(diào)節(jié)劑 (AIM)，可激活 Nrf2 并抑制氧化氮 (NO)。IC50 & Target Nrf2 1體外研究 To evaluate the anti-in

4、flammatory activity of RTA-408, RAW 264.7 mouse macrophage cells are treated withRTA-408 for two hours and then IFN is added to stimulate NO production and release into the media. RTA-408 dose-dependently reduces NO concentrations in the media with an IC50 value of 4.41.8 nM. Thepotency of RTA-408 i

5、n this assay is similar to that of Bardoxolone methyl, which has an IC50 value of 1.90.8nM. Nrf2 activation is required for AIM-mediated NO suppression. A decrease in nitric oxide synthase 2(Nos2) protein levels is observed in bardoxolone methyl-treated RAW 264.7 cells, which is attenuated whenNrf2

6、mRNA levels are reduced by siRNA. To evaluate the anticancer activity of RTA-408, a panel of eighthuman cell lines derived from tumors of different origin are treated with RTA-408 and measured cell growth72 hours later using the sulforhodamine B (SRB) assay. RTA-408 inhibits the growth of all tumor

7、lines with anaverage GI50 value of 26074 nM. To determine whether RTA-408 induces apoptosis, the panel of tumorcells are treated with RTA-408 and the caspase substrate, DEVD-AFC, for 24 hours. RTA-408 dose-dependently increases DEVD-AFC cleavage, indicating that RTA-408 treatment triggers caspase ac

8、tivationin cancer cells. Caspase-3 and caspase-9 cleavage is also observed by western blot at the sameconcentrations of RTA-408 that increases DEVD-AFC cleavage 1.體內(nèi)研究 To determine whether RTA-408 is an effective mitigator of hematopoietic acute radiation syndrome afterbone marrow-lethal doses of to

9、tal-body irradiation (TBI), mice are administered 3 daily injections of 17.5mg/kg RTA-408 beginning 24 h after TBI. Teatment with RTA-408 results in the 35 day survival of 100% of 7Gy (LD40/35) TBI mice (P100/13) TBI mice (P 2.PROTOCOLCell Assay 1 MEFs, PANC-1, A549, A375, A549/NF-B-Luc and HeLa/NF-

10、B-Luc cells are cultured in Gibco high glucoseDMEM with 10% FBS. G-361 cells are cultured in McCoys 5A medium with 10% FBS. All other cell lines arecultured in RPMI 1640 medium with 10% FBS. For growth inhibition assays, cells are plated in duplicate 96-well culture dishes at 3103 cells per well. Th

11、e following day, one plate is treated with RTA-408 (200, 400,600, 800 and 1000 nM) and the other is immediately processed for the sulforhodamine B (SRB) assay (time0). Cells in the RTA-408-treated plate are processed for the SRB assay 72 hours after the start of treatment.Percentage of growth relati

12、ve to vehicle-treated cells is calculated. Dose-response curves are plotted inGraphPad Prism and GI50 values are calculated. For cell counting experiments, MEFs are plated in 6-wellculture dishes at 5104 cells per well and treated with RTA-408 the following day. Following treatment, cellsare counted

13、 using a Vi-CELL XR cell analyzer. For clonogenic assays, wild-type (1103 cells per well) andKeap1-/- (0.5103 cells per well) MEFs are seeded in 6-well dishes. Six hours later, MEFs are treated withRTA-408. After seven days, colonies are fixed with a 1:7 solution of acetic acid:MeOH and stained with

14、 0.5%crystal violet in MeOH. Colonies consisting of 50 cells are counted 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 22/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEAdministration 2 For radiation survival experiments, wild-type C57Bl

15、/6 CD45.2 mice (6-8 weeks old) are used. Congenic wild-type C57Bl/6 CD45.1 and C57Bl/6 CD45.1/CD45.2 hybrid host mice are used as recipients in transplantationexperiments. RTA-408 stock solutions for vehicle control (DMSO) are prepared within 1 h before injection.RTA-408 (17.5 mg/kg) or DMSO is admi

16、nistered intraperitoneally at 24, 48 and 72 h after irradiation. Whole-body irradiation (7-8 Gy) is performed using a 250-kVp X-ray machine with 50 cm source-to-skin distanceand a 2 mm copper filter. The dose rate is approximately 1.4 Gy/min.MCE has not independently confirmed the accuracy of these

17、methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Oxid Med Cell Longev. 2017;2017:7612182. Inflammation. 2019 Jun 29.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Probst BL, et al. RTA 408, A Novel Synthetic Triterpenoid with Broad Anticancer and Anti-Inflammatory Activity. PLoS One. 2015 Apr21;10(4):e0122942.2. Goldman DC, et al. The triterpenoid RTA 408 is a robust mitigator of hematopoietic acute radiation syndrome in mice. Radiat Res. 2015Mar;183(3):338-443. Peng Han, et al. RTA-408 Protects Kidney from Ischemia-Reperfusion Injury in Mice via Activating Nrf2 and