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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C25H23ClN2O3 |
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分子量 | 434.91 | CAS No. | 1300031-52-0 | |
Solubility (25°C)* | 体外 | 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. |
製品説明 | 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. |
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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] |
キナーゼアッセイ | Determination of BET Protein Binding Affinities to I-BET726 | |
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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. | ||
細胞アッセイ | 細胞株 | 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 |
濃度 | ~10 μM | |
反応時間 | 6 days | |
実験の流れ | 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. | |
動物実験 | 動物モデル | Xenograft models of non-MYCN-amplified and MYCN-amplified neuroblastoma in immunocompromised mice using the SK–N-AS and CHP-212 cell lines |
投薬量 | 15 mg/kg once daily | |
投与方法 | p.o. |
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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 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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