1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEIMD-0354Cat. No.: HY-10172CAS No.: 978-62-1Synonyms: IKK2 Inhibitor V分式: CHClFNO分量: 383.67作靶點: IKK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 : 100 mg/mL (260.64 mM)H2O : 40% PEG

2、300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.52 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (6.52 mM); Suspended solution; Need ultrasonicBIOLOGICAL ACTIVITY物活性 IMD-0354種選擇性 IKK 抑制劑，抑制 NF-B 活性。IMD035

3、4 抑制 TNF- 誘導(dǎo)的 NF-B 轉(zhuǎn)錄活性，IC 50 為 1.20.3 M。IC50 & Target IKK NF-B1.2 M (IC50)體外研究 IMD-0354 inhibits NF-B activity in HMC-1 cells, resulting in complete repression of growth factor-independent proliferation of mast cells. When the DNA-binding activity of NF-B is inhibited by treatment withIMD-0354, cel

4、l proliferation is completely suppressed. HMC-1 cells are incubated with increasingconcentrations of IMD-0354 or STI571 for 24, 48, and 72 hours, and numbers and viability of cells aredetermined by a dye exclusion test and an MTT assay. IMD-0354 suppresses cell proliferation in a time- anddose-depen

5、dent manner. The inhibitory effect of IMD-0354 is remarkable, even at lower concentrations,when compared with that of STI571 1. IMD0354 inhibits TNF- induced NF-B transcription activity with anIC 50 of 1.20.3 uM 2.體內(nèi)研究 Daily administration with 5 mg/kg IMD-0354 significantly suppresses tumor expansi

6、on in nude miceimplanted with established MDA-MB-231 tumors. In mice treated with IMD-0354, tumor progression isrestrained 3. The number of infiltrating cells in aqueous humor is 53.69.8105, 72.517.0105,127.2532.0105, and 132.025.0105 cells/mL in rats treated with 30, 10, 3, or 0 mg/kg of IMD-0354,r

7、espectively. The total protein concentrations of aqueous humor are 92.63.1 mg/mL, 101.56.8 mg/mL,112.61.9 mg/mL, and 117.331.8 mg/mL in rats treated with 30, 10, 3, and 0 mg/kg of IMD-0354,respectively 4.PROTOCOLCell Assay 1 HMC-1 cells (2105 cells/mL) are incubated with various concentrations of IM

8、D-0354 (0.1, 0.5, 1, 5 and 10uM), STI571, or pyrrolidine dithiocarbamate (PDTC) for the indicated hours, and viable cell numbers arecalculated with the use of the trypan blue dye exclusion test at each time point. Cells (2105 cells/mL) areincubated in phenol red free -MEM containing 10% FCS (for HMC

9、-1 and IC-2 cells) or 5% FCS (forCBhCMCs), and antibiotics with or without various concentrations of IMD-0354 (0.1, 0.5, 1, 5 and 10 uM),STI571, or PDTC. IC-2WT cells and CBhCMCs are incubated in the presence of 100 ng/mL recombinant rator recombinant human SCF. One hundred microliters of cell suspe

10、nsion is applied to each well of 96-wellculture plates and are incubated for 24, 48, and 72 hours. Before 4 hours from the end of the culture, 10 Lof 5 mg/mL MTT dissolved in PBS is added to each well. The reaction is stopped with the addition of 100 Lof 10% SDS in 0.01 N HCl. Absorbance is measured

11、 at 577 nm with ImmunoMini NJ-2300 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 32/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEAdministration 34 MDA-MB-231 cells are suspended in PBS (5106 cells/100 L mouse) and s.c. injected to the

12、back of femaleBALB/c nude mice at the age of 4 to 5 weeks. After growth, the tumor is removed surgically and 100 mg ofeach established tumor is transplanted to the back of other female nude mice at the age of 4 weeks underether anesthesia. IMD-0354 is suspended in saline and 5 mg/kg body weight IMD-

13、0354 (suspended in 100 L/mouse) is given to each mouse by i.p. injection once a day for 28 days after the implantation. Saline isinjected in nude mice as a control. Estimated tumor volume (mm3) and tumor weight (mg) are calculated.Rats 4Eight-week-old male Lewis rats (180-220 g) are used. Endotoxin-

14、induced uveitis (EIU) is induced withsubcutaneous injection with 200 g LPS from Escherichia coli that has been diluted in 200 L PBS. At thesame time, the rats are injected intraperitoneally with 30, 10, or 3 mg/kg of IMD-0354, diluted in 500 L of0.5% CMC. Control EIU rats are intraperitoneally admin

15、istered 500 L of CMC alone. Nave rats are used ascontrols. All experiments are performed in triplicate with five animals in each group.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) Biochim Biophys Acta Mol Basis Dis. 2019 Jun 26;1865(10):2

16、618-2632. Vascular. 2018 Dec;26(6):634-640.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Tanaka A, et al. A novel NF-kappaB inhibitor, IMD-0354, suppresses neoplastic proliferation of human mast cells with constitutivelyactivated c-kit receptors. Blood. 2005 Mar 15;105(6):232

17、4-31.2. Li YR, et al. Study of the inhibitory effects on TNF-induced NF-B activation of IMD0354 analogs. Chem Biol Drug Des. 2017Dec;90(6):1307-1311.3. Tanaka A, et al. A new IkappaB kinase beta inhibitor prevents human breast cancer progression through negative regulation of cell cycletransition. Cancer Res. 2006 Jan 1;66(1):419-26.4. Lennikov A, et al. Amelioration of endotoxin-induced uveitis treated