GSK1324726A (I-BET726)

Catalog No.S7620 Batch:S762002

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Technical Data

Formula

C25H23ClN2O3
Molecular Weight 434.91 CAS No. 1300031-52-0
Solubility (25°C)* In vitro DMSO 87 mg/mL (200.04 mM)
Ethanol 87 mg/mL (200.04 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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 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]
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]

Protocol (from reference)

Kinase Assay:[1]
  • 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 Assay:[1]
  • 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.
Animal Study:[1]
  • 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.

Selleck's GSK1324726A (I-BET726) has been cited by 7 publications

Inhibition of OTUB2 suppresses colorectal cancer cell growth by regulating β-Catenin signaling [ Am J Cancer Res, 2023, 13(11):5382-5393] PubMed: 38058843
BET and CDK Inhibition Reveal Differences in the Proliferation Control of Sympathetic Ganglion Neuroblasts and Adrenal Chromaffin Cells [ Cancers (Basel), 2022, 14(11)2755] PubMed: 35681734
Synergistic Anti-Tumor Effect of Combining Selective CDK7 and BRD4 Inhibition in Neuroblastoma [ Front Oncol, 2021, 11:773186] PubMed: 35198433
Isoform-specific Involvement of Brpf1 in Expansion of Adult Hematopoietic Stem and Progenitor Cells [ J Mol Cell Biol, 2020, 11;12(5):359-371] PubMed: 31565729
BORIS promotes chromatin regulatory interactions in treatment-resistant cancer cells [ Nature, 2019, 10.1038/s41586-019-1472-0] PubMed: 31391581
BRD4 Inhibition Is Synthetic Lethal with PARP Inhibitors through the Induction of Homologous Recombination Deficiency. [ Cancer Cell, 2018, 33(3):401-416] PubMed: 29533782
Epigenetic Reprogramming with Antisense Oligonucleotides Enhances the Effectiveness of Androgen Receptor Inhibition in Castration-Resistant Prostate Cancer [ Cancer Res, 2018, 78(20):5731-5740] PubMed: 30135193

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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