ML385 _Keap1-Nrf2 抑制劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEML385Cat. No.: HY-100523CAS No.: 846557-71-9分式: CHNOS分量: 511.59作靶點: Keap1-Nrf2作通路: NF-B儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 30 mg/mL (58.64 mM)* means soluble, but saturation unk

2、nown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.9547 mL 9.7735 mL 19.5469 mL5 mM 0.3909 mL 1.9547 mL 3.9094 mL10 mM 0.1955 mL 0.9773 mL 1.9547 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備液，并請注意儲備液的保存式和期限。體內(nèi)實驗 請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍福渲魄罢埾扰渲瞥吻宓膬湟?，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當天使；澄清的儲備液可以根據(jù)儲存條件，適當保存；

3、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 (4.89 mM); Clear solutionBIOLOGICAL ACTIVITY1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE物活性 ML385是特異的 NRF2 抑制劑，IC50 為1.9 M。IC50 & Target IC50: 1.9 M (NRF2) 1體外研究 ML385 interacts with NRF2 and affects the DNA bin

4、ding activity of the NRF2-MAFG protein complex. Theaddition of ML385 decreases anisotropy in a dose-dependent manner, with an IC50 of 1.9 M. A dose-dependent reduction in the NRF2 transcriptional activity is observed and the maximum inhibitory concentrationis 5 M by ML385. Treatment with ML385 leads

5、 to a significant reduction in NRF2 and downstream targetgene expression selectively in KEAP1 mutant H460 cells. ML385 selectively affects the colony forming abilityor growth of lung cancer cells with gain of NRF2 function 1.體內(nèi)研究 ML385 in combination with carboplatin leads to a significant reduction

6、 in tumor cell proliferation, demonstratedby fewer Ki-67 positive cells. Tumor samples treated with ML385 show a significant reduction in NRF2 proteinlevel and its downstream target genes 1.PROTOCOLCell Assay 1 cells are treated with ML385 for 36 h. An equal amount of CellTiter-Blue reagent is added

7、 to the wells andthe fluorescence is measured after 30 min. The CellTiter-Blue reagent is discarded and the Caspase-Glo(100 L) reagent is added to the cells and incubated at 37C for an additional 60-90 min. The resultingluminescence is recorded and the caspase activity is normalized to cell number 1

8、.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: Mice tumor xenografts are randomly allocated into 4 groups: vehicle, ML385, carboplatin, and ML385Administration 1 in combination with carboplatin. Vehicle, carboplatin (5 mg/kg daily Monday

9、to Friday)18, ML385 (30 mg/kgdaily Monday to Friday), or ML385 in combination with carboplatin are administered intraperitoneally for 3weeks. At the end of treatment period, mice are sacrificed and the tumor, blood, lung, and liver samples arecollected 1.MCE has not independently confirmed the accur

10、acy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Nat Commun. 2018 Oct 24;9(1):4429. Br J Pharmacol. 2018 Oct;175(19):3747-3757. Free Radic Biol Med. 2019 Aug 13. pii: S0891-5849(19)30749-X. Free Radic Biol Med. 2018 Dec 30;134:23-41. J Exp Clin Cancer Res. 2018 Dec 20;37(1):321.See more

11、 customer validations on HYPERLINK / www.MedChemEREFERENCES1. Singh A, et al. Small Molecule Inhibitor of NRF2 Selectively Intervenes Therapeutic Resistance in KEAP1-Deficient NSCLC Tumors.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEACS Chem Biol. 2016 Nov 18;11(11):3214-3225.2. Xinnong Liu, et al. Isoliquiritigenin ameliorates acute pancreatitis in mice via inhibition of oxidative stress and modulation of the Nrf2/HO-1 pathway. Oxid Med Cell Longev. 20 March 2018.McePdfHeightCaution: Product