GSK1324726A (I-BET726)

製品コードS7620 バッチS762002

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₅H₂₃ClN₂O₃

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

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	2.500mg/ml (5.75mM)	Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	2.500mg/ml (5.75mM)	Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	GSK1324726A (I-BET726) は、BETファミリータンパク質の高選択的阻害剤であり、BRD2、BRD3、BRD4に対するIC50はそれぞれ41 nM、31 nM、22 nMです。
in vitro	In neuroblastoma cell lines, GSK1324726A (I-BET726) inhibits cell growth and induces cytotoxicity. It also modulates expression of genes involved in apoptosis, signaling, and MYC-family pathways, including the direct suppression of BCL2 and MYCN.
in vivo	In the mouse SK–N-AS and CHP-212 models, GSK1324726A (I-BET726) (15 mg/kg p.o.) results in tumor growth inhibition and down-regulation of MYCN and BCL2 expression. In a mouse septic shock model, this compound (10 mg/kg i.v.) shows potent anti-inflammatory effects and prevents death of diseased animals.

プロトコル(参考用のみ)

キナーゼアッセイ	Determination of BET Protein Binding Affinities to I-BET726
キナーゼアッセイ	For determination of binding affinities to BET protein bromodomains, GSK1324726A (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 (λ_EX = 337 nm, λ_EM = 615 nm, λ_EM = 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 GSK1324726A (I-BET726). After incubating the cells for 6 days and developing as described above, results are plotted as a percentage of the T0 value, normalized to 100%, versus concentration of this 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.

参考

https://pubmed.ncbi.nlm.nih.gov/24009722/
https://pubmed.ncbi.nlm.nih.gov/25249180/

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

BET inhibition revealed varying MYC dependency mechanisms independent of gene alterations in aggressive B-cell lymphomas [ Clin Epigenetics, 2024, 16(1):185]	PubMed: 39702340
Inhibition of OTUB2 suppresses colorectal cancer cell growth by regulating β-Catenin signaling [ Am J Cancer Res, 2023, 13(11):5382-5393]	PubMed: 38058843
Exploration de la réponse moléculaire à l'inhibition des protéines BET dans les lymphomes B réfractaires [ HAL OPEN SCIENCE, 2023, ]	PubMed: None
The epigenetic roles of BET inhibitors JQ1 and I-BET726 in regulating inflammation and treatment for experimental autoimmune encephalomyelitis [ Authorea Preprints, 2023, ]	PubMed: None
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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。