Home Epigenetics Epigenetic Reader Domain inhibitor GSK1324726A (I-BET726) For research use only.

GSK1324726A (I-BET726)

GSK1324726A (I-BET726) is a highly selective inhibitor of BET family proteins with IC50 of 41 nM, 31 nM, and 22 nM for BRD2, BRD3, and BRD4, respectively.

GSK1324726A (I-BET726) Chemical Structure

GSK1324726A (I-BET726) Chemical Structure

CAS No. 1300031-52-0

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GSK1324726A (I-BET726) Related Products

Signaling Pathway

Epigenetic Reader Domain Signaling Pathways

Epigenetic Reader Domain Signaling Pathway

Biological Activity

Description GSK1324726A (I-BET726) is a highly selective inhibitor of BET family proteins with IC50 of 41 nM, 31 nM, and 22 nM for BRD2, BRD3, and BRD4, respectively.
Targets
BRD4 [1]
(Cell-free assay)		 BRD3 [1]
(Cell-free assay)		 BRD2 [1]
(Cell-free assay)
22 nM 31 nM 41 nM
In vitro
In vitro In neuroblastoma cell lines, GSK1324726A inhibits cell growth and induces cytotoxicity. GSK1324726A also modulates expression of genes involved in apoptosis, signaling, and MYC-family pathways, including the direct suppression of BCL2 and MYCN. [1]
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.
Cell Research Cell lines LA-N-1, Kelly, LA1-55n, BE(2)-M17, BE(2)-C, KanTS, IMR32, LA-N-2, SK-N-SH, SK-N-BE(2), CHP-134, SK-N-AS, SH-SY5Y, SK-N-FI, CHP-212, LA1-5s, SK-N-DZ cells
Concentrations ~10 μM
Incubation Time 6 days
Method 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.
In Vivo
In vivo In the mouse SK–N-AS and CHP-212 models, GSK1324726A (15 mg/kg p.o.) results in tumor growth inhibition and down-regulation MYCN and BCL2 expression. [1] In a mouse septic shock model, GSK1324726A (10 mg/kg i.v.) shows potent anti-inflammatory effects, and prevents death of diseased animals. [2]
Animal Research Animal Models Xenograft models of non-MYCN-amplified and MYCN-amplified neuroblastoma in immunocompromised mice using the SK–N-AS and CHP-212 cell lines
Dosages 15 mg/kg once daily
Administration p.o.

Chemical Information & Solubility

Molecular Weight 434.91 Formula

C25H23ClN2O3
CAS No. 1300031-52-0 SDF Download GSK1324726A (I-BET726) SDF
Smiles CC1CC(C2=C(N1C(=O)C)C=CC(=C2)C3=CC=C(C=C3)C(=O)O)NC4=CC=C(C=C4)Cl
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 86 mg/mL ( (197.74 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 86 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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