| 名稱 | GSK1324726A |
| 描述 | GSK1324726A (I-BET726) is a greatly specific inhibitor of BET family proteins for BRD2(IC50=41 nM), BRD3(IC50=31 nM), and BRD4 (IC50=22 nM). |
| 細胞實驗 | Briefly, cells are seeded into 384-well or 96-well plates at a density optimized for 6 days of growth. The following day, T0 measurements are taken using CellTiter-Glo, CellTiter-Fluor, or CyQuant Direct, following the manufacturer's instructions. Plates are read on an Envision, Safire 2, or SpectraMax Gemini EM plate reader. Remaining plates are treated with DMSO or a titration of I-BET726. Cells are incubated for 6 days and developed as described above. Results are plotted as a percentage of the T0 value, normalized to 100%, versus concentration of compound. A 4-parameter equation is used to generate concentration response curves. Growth IC50 (gIC50) values are calculated at the mid-point of the growth window (between DMSO and T0 values). Ymin-T0 values are calculated by subtracting the T0 value (100%) from the Ymin value on the curve, and are a measure of net population cell growth or death.(Only for Reference) |
| 激酶實驗 | Determination of BET Protein Binding Affinities to I-BET726: For determination of binding affinities to BET protein bromodomains, I-BET726 is titrated against truncates containing both BD1 and BD2 of BRD2 (10 nM), BRD3 (10 nM), and BRD4 (10 nM) in 50 mM HEPES pH7.5, 150 mM NaCl, 5% Glycerol, 1 mM DTT and 1 mM CHAPS in the presence of an Alexa 647 derivative (50 nM) of fluorescent ligand. After equilibrating for 1 h, the bromodomain protein: ligand interaction is detected using Time Resolved Fluorescence Resonance Energy Transfer (TR-FRET) following the addition of 1.5 nM europium chelate labeled anti-6His antibody. Plates are read using an Envision Plate reader (λEX = 337 nm, λEM = 615 nm, λEM = 665 nm; dual dichroic = 400 nm & 630 nm). These data are fitted to a four parameter IC50 model using Graphit data analysis software. |
| 體外活性 | 在小鼠SK-N-AS和CHP-212模型中, GSK1324726A（15 mg/kg o.p.）抑制腫瘤生長,并下調(diào)MYCN 和 BCL2的表達.在小鼠感染性休克模型中,GSK1324726A（10 mg/kg i.v. ）表現(xiàn)出有效的抗炎作用,并防止患病動物的死亡. |
| 體內(nèi)活性 | 在神經(jīng)母細胞瘤細胞系中,GSK1324726A抑制細胞生長并誘導細胞毒性。GSK1324726A能夠調(diào)節(jié)MYC家族通路的基因表達,包括BCL2 和 MYCN的直接表達。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 50 mg/mL (114.97 mM)
Ethanol : 80 mg/mL (183.9 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| 關(guān)鍵字 | GSK-1324726A | Apoptosis | I-BET-726 | Inhibitor | Epigenetic Reader Domain | inhibit | GSK1324726A | I-BET 726 |
| 相關(guān)產(chǎn)品 | L-Glutamic acid | Metronidazole | 5-Fluorouracil | Curcumin | Dextran sulfate sodium salt (MW 4500-5500) | Stavudine | Tributyrin | Myricetin | L-Ascorbic acid | Acetylcysteine | Salicylic acid | Sodium 4-phenylbutyrate |
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