I-BET151 (GSK1210151A)

Catalog No.S2780 Batch:S278001

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Technical Data

Formula

C23H21N5O3
Molecular Weight 415.44 CAS No. 1300031-49-5
Solubility (25°C)* In vitro DMSO 83 mg/mL (199.78 mM)
Ethanol 27 mg/mL (64.99 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 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.
Targets
BRD3 [1]
(Cell-free assay)		 BRD2 [1]
(Cell-free assay)		 BRD4 [1]
(Cell-free assay)
0.25 μM 0.5 μM 0.79 μM
In vitro I-BET151 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), I-BET151 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. I-BET151 (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. I-BET151 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, I-BET151 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. I-BET151 treatment 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 Administration of I-BET151 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]
Features 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.

Protocol (from reference)

Kinase Assay:

[1]
  • Fluorescence anisotropy (FP) ligand displacement assay

    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 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).
Cell Assay:

[1]
  • Cell lines

    MV4;11, MOLM13, NOMO1, RS4;11, HEL, HL60 and K562

  • Concentrations

    Dissolved in DMSO, final concentrations ~100 μM

  • Incubation Time

    24, or 72 hours

  • Method

    Cells are exposed to various concentrations of I-BET151 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
Animal Study:

[1]
  • Animal Models

    NOD-SCID mice injected intravenously with MV4;11 cells, and C57BL/6 mice injected intravenously with MLL-AF9 cells

  • Dosages

    ~30 mg/kg/day

  • Administration

    Intraperitoneal injection

Customer Product Validation

Data from [Data independently produced by , , Theranostics, 2016, 6(2):219-30.]

Data from [Data independently produced by , , Oncotarget, 2016, 7(3):2545-54]

Data from [Data independently produced by , , J Immunol, 2018, 201(9):2744-2752]

Data from [Data independently produced by , , Front Pharmacol, 2018, 9:1166]

Selleck's I-BET151 (GSK1210151A) has been cited by 57 publications

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
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
RUNX1 colludes with NOTCH1 to reprogram chromatin in T cell acute lymphoblastic leukemia [ iScience, 2023, 26(6):106795] PubMed: 37213235
RUNX1 colludes with NOTCH1 to reprogram chromatin in T cell acute lymphoblastic leukemia [ iScience, 2023, 26(6):106795] PubMed: 37213235
Enhancer Clusters Drive Type I Interferon-Induced TRAIL Overexpression in Cancer, and Its Intracellular Protein Accumulation Fails to Induce Apoptosis [ Cancers (Basel), 2023, 15(3)967] PubMed: 36765925
A CRISPR Screen of HIV Dependency Factors Reveals That CCNT1 Is Non-Essential in T Cells but Required for HIV-1 Reactivation from Latency [ Viruses, 2023, 15(9)1863] PubMed: 37766271
A CRISPR Screen of HIV Dependency Factors Reveals That CCNT1 Is Non-Essential in T Cells but Required for HIV-1 Reactivation from Latency [ Viruses, 2023, 15(9)1863] PubMed: 37766271

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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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