| Name | GSK1324726A |
| Description | 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). |
| Cell Research | 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) |
| Kinase Assay | 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. |
| In vitro | In the mouse models SK-N-AS and CHP-212, GSK1324726A administered at 15 mg/kg orally (o.p.) was effective in inhibiting tumor growth and downregulating the expression of MYCN and BCL2. Additionally, at a dosage of 10 mg/kg intravenously (i.v.), GSK1324726A demonstrated potent anti-inflammatory effects and prevented mortality in mice experiencing septic shock. |
| In vivo | In neuroblastoma cell lines, GSK1324726A inhibits cell growth and induces cytotoxicity. It regulates the expression of genes in the MYC family pathway, including direct expression of BCL2 and MYCN. |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | DMSO : 50 mg/mL (114.97 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (4.6 mM), Sonication is recommended.
Ethanol : 80 mg/mL (183.95 mM), Sonication is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| Keywords | Inhibitor | inhibit | I-BET-726 | I-BET 726 | GSK-1324726A | GSK1324726A | EpigeneticReaderDomain | Epigenetic Reader Domain | BRD4 | BRD3 | BRD2 | Apoptosis |
| Inhibitors Related | Stavudine | Aceglutamide | Urea | Tamoxifen | Cysteamine hydrochloride | Metronidazole | Citric Acid Triammonium | Formamide | Dimethyl phthalate | Alginic acid | Sodium Molybdate | Sildenafil citrate |
| Related Compound Libraries | Highly Selective Inhibitor Library | Reprogramming Compound Library | Histone Modification Compound Library | Bioactive Compound Library | Epigenetics Compound Library | Chromatin Modification Compound Library | Inhibitor Library | NO PAINS Compound Library | PPI Inhibitor Library | Anti-Aging Compound Library | Bioactive Compounds Library Max | Anti-Cancer Compound Library |
United States
