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受注：045-509-1970 |
技術サポート：tech@selleck.co.jp 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
化学情報
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C23H21N5O3 |
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| 分子量 | 415.44 | CAS No. | 1300031-49-5 | |
| Solubility (25°C)* | 体外 | DMSO | 83 mg/mL (199.78 mM) | |
| Ethanol | 83 mg/mL (199.78 mM) | |||
| Water | Insoluble | |||
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* <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. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | I-BET151 (GSK1210151A) is a novel selective BET inhibitor for BRD2, BRD3 and BRD4 with IC50 of 0.5 μM, 0.25 μM, and 0.79 μM in cell-free assays, respectively. |
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| in vitro | I-BET151 (GSK1210151A) exhibits potent selectivity over an extensive range of diverse protein types such as COX-2, P450, Aurora B, GSK3β, PI3K-γ, GPCR, ion channels, and transporters. Similar to I-BET762 (GSK525762A), it displays potent binding affinity to BRD2, BRD3 and BRD4 with KD of 0.02-0.1 μM, and significantly inhibits lipopolysaccharide-stimulated IL-6 cytokine production in human peripheral blood mononuclear cells (PBMC) and whole blood (WB) as well as rat WB with IC50 of 0.16 μM, 1.26 μM, and 1.26 μM, respectively. This compound (0.5 or 5 μM) inhibits the binding of BETs (BRD2, BRD3, BRD4, and BRD9) but not the binding of 23 other bromodomain proteins in HL60 nuclear extract to acetylated histone peptides. It has potent efficacy against cell lines harboring different MLL-fusions such as MV4;11, RS4;11, MOLM13, and NOMO1 cells with IC50 of 15-192 nM. Consistently, it completely ablates the colony-forming potential of MLL-fusion-driven leukaemias (MOLM13) but not leukaemias driven by tyrosine kinase activation (K562). I-BET151 also displays potent efficacy in both liquid culture and clonogenic assays using primary murine progenitors transformed with either MLL-ENL or MLL-AF9. Treatment with this compound significantly induces apoptosis and prominent G0/G1 arrest in MLL-fusion cell lines driven by distinct MLL fusions (MOLM13 and MV4;11 containing MLL-AF9 and MLL-AF4, respectively) but not the K562 cells, probably due to the inhibition of transcription of BCL2, C-MYC and CDK6 by blocking the recruitment of BRD3/4, PAFc and SEC components into transcriptional start site (TSS). [1] |
| in vivo | I-BET151 (GSK1210151A), when administered at 30 mg/kg/day, significantly inhibits tumor growth of murine MLL-AF9 and human MLL-AF4 leukaemia in mice, and provides marked survival benefit. [1] |
| 特徴 | Optimized to retain excellent BET target potency and selectivity while enhancing the in vivo pharmacokinetics and terminal half-life to enable prolonged in vivo studies. |
プロトコル(参考用のみ)
| キナーゼアッセイ | Fluorescence anisotropy (FP) ligand displacement assay | |
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| All components are dissolved in buffer of composition 50 mM HEPES pH 7.4, 150 mM NaCl and 0.5 mM CHAPS with final concentrations of BRD 2/3/4 75 nM, fluorescent ligand 5 nM. 10 μL of this reaction mixture is added using a micro multidrop to wells containing 100 nL of various concentrations of I-BET151 (GSK1210151A) or DMSO vehicle (1% final) in Greiner 384 well Black low volume microtitre plate and equilibrated in the dark for 60 minutes at room temperature. Fluorescence anisotropy is read in Envision (lex = 485 nm, lEM = 530 nm; Dichroic = 505 nM). | ||
| 細胞アッセイ | 細胞株 | MV4;11, MOLM13, NOMO1, RS4;11, HEL, HL60 and K562 |
| 濃度 | Dissolved in DMSO, final concentrations ~100 μM | |
| 反応時間 | 24, or 72 hours | |
| 実験の流れ | Cells are exposed to various concentrations of I-BET151 (GSK1210151A) for 24 or 72 hours in 384-well or 96-well plates. For cell growth inhibition assays, plates are added with CellTiter-Glo reagent using a volume equivalent to the cell culture volume in the wells, shaken for approximately 2 minutes and chemiluminescent signal is read on the Analyst GT or EnVision Plate Reader. For cell proliferation assays, CellTiter-Aqueous One is added to each well and plates are incubated for 4 hours at 37 °C. Absorbance is read at 490 nm on a SpectraMax Gemini reader |
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| 動物実験 | 動物モデル | NOD-SCID mice injected intravenously with MV4;11 cells, and C57BL/6 mice injected intravenously with MLL-AF9 cells |
| 投薬量 | ~30 mg/kg/day | |
| 投与方法 | Intraperitoneal injection | |
参考
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カスタマーフィードバック
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Data from [Data independently produced by , , Theranostics, 2016, 6(2):219-30.]
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Data from [Data independently produced by , , Oncotarget, 2016, 7(3):2545-54]
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Data from [Data independently produced by , , J Immunol, 2018, 201(9):2744-2752]
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：
| Integrator complex subunit 12 knockout overcomes a transcriptional block to HIV latency reversal [ Elife, 2025, 13RP103064] | PubMed: 40207620 |
| A targeted CRISPR screen identifies ETS1 as a regulator of HIV-1 latency [ PLoS Pathog, 2025, 21(4):e1012467] | PubMed: 40198713 |
| Development and Validation of an HPLC-MS/MS Method for Determining I-BET151 in Rat Plasma and Its application to Pharmacokinetic Studies [ Drug Des Devel Ther, 2025, 19:8679-8689] | PubMed: 41030777 |
| A screen of chromatin-targeting compounds identifies TAF1 as a novel regulator of HIV latency [ bioRxiv, 2025, 2025.05.24.655900] | PubMed: 40475469 |
| Synergy of retinoic acid and BH3 mimetics in MYC(N)-driven embryonal nervous system tumours [ Br J Cancer, 2024, 10.1038/s41416-024-02740-5] | PubMed: 38942989 |
| Direct reprogramming of fibroblasts into spiral ganglion neurons by defined transcription factors [ Cell Prolif, 2024, e13775.] | PubMed: 39551613 |
| Analysis of synthetic cellular barcodes in the genome and transcriptome with BARtab and bartools [ Cell Rep Methods, 2024, S2667-2375(24)00094-8] | PubMed: 38670101 |
| Integrator complex subunit 12 knockout overcomes a transcriptional block to HIV latency reversal [ bioRxiv, 2024, 2024.08.30.610517] | PubMed: 39257755 |
| A Crispr Screen of HIV Dependency Factors to Identify Host Proteins Necessary for Activation of Latent HIV Proviruses [ ResearchWorks Archive, 2024, ] | PubMed: none |
| Inhibition of neutral sphingomyelinase 2 impairs HIV-1 envelope formation and substantially delays or eliminates viral rebound [ Proc Natl Acad Sci U S A, 2023, 120(28):e2219543120] | PubMed: 37406092 |
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。