GSK1324726A 是一种选择性有效的BET蛋白抑制剂，高亲和力结合到BRD2、BRD3和BRD4，IC50值分别为 41 nM、31 nM和 22 nM。

GSK1324726A is a greatly specific inhibitor of BET family proteins for BRD2(IC50=41 nM), BRD3(IC50=31 nM), and BRD4 (IC50=22 nM).

在小鼠SK-N-AS和CHP-212模型中, GSK1324726A（15 mg/kg o.p.）抑制肿瘤生长,并下调MYCN 和 BCL2的表达.在小鼠感染性休克模型中,GSK1324726A（10 mg/kg i.v. ）表现出有效的抗炎作用,并防止患病动物的死亡.

在神经母细胞瘤细胞系中,GSK1324726A抑制细胞生长并诱导细胞毒性。GSK1324726A能够调节MYC家族通路的基因表达,包括BCL2 和 MYCN的直接表达。

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.

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)

1300031-52-0

C25H23ClN2O3

434.92

I-BET726

Ethanol:80 mg/mL (183.9 mM)
DMSO:80 mg/mL (183.9 mM)
H2O:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years