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    InvivoChem Cat #: V0421
    CAS #: 1395084-25-9Purity ≥98%

    Description: MS436 (MS-346), a diazobenzene analog, is a novel, potent and selective inhibitor of BET/BRD4 bromodomain with potential anti-inflammatory activity. It inhibits BRD4 (1) and BRD4 (2) with Ki values of <0.085 μM and 0.34 μM, respectively. MS 436 effectively inhibits NF-κB-directed production of nitric oxide/NO and proinflammatory cytokine interleukin-6 (IL-6) in murine macrophages.  

    References: J Med Chem. 2013 Nov 27;56(22):9251-64.

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    • VE
    • OF
    • YALE
    • hhmi
    • 香港大学
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    Molecular Weight (MW)383.42
    CAS No.1395084-25-9
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 55 mg/mL (143.4 mM)
    Water: <1 mg/mL
    Ethanol:  1 mg/mL (2.6 mM)
    Other info

    Chemical Name: (E)-4-[2-(2-Amino-4-hydroxy-5-methylphenyl)diazenyl]-N-2-pyridinylbenzenesulfonamide


    InChi Code: InChI=1S/C18H17N5O3S/c1-12-10-16(15(19)11-17(12)24)22-21-13-5-7-14(8-6-13)27(25,26)23-18-4-2-3-9-20-18/h2-11,24H,19H2,1H3,(H,20,23)/b22-21+

    SMILES Code: O=S(C1=CC=C(/N=N/C2=CC(C)=C(O)C=C2N)C=C1)(NC3=NC=CC=C3)=O

    SynonymsMS-436; MS 436; MS436.

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    In Vitro

    In vitro activity: As a chemical probe for BRPF bromodomains, OF-1 increases thermal stability in the cellular thermal shift assay of full length BRPF1B at 1 μM and also demonstrates accelerated FRAP recovery at 5 μM in the BRPF2 FRAP assay. In addition, OF-1 shows modest general cytotoxicity.

    Kinase Assay: Binding affinity of the newly synthesized diazobenzene compounds (e.g., MS436) for various bromodoamins is assessed in a fluorescence anisotropy competition assay using a fluorescein isothiocyanate (FITC)-labeled MS417 as an assay probe. Competition experiments are performed with a BrD protein (0.25-1 µM) and the fluorescent probe (80 nM), and increasing concentration of unlabeled competing ligand in a PBS buffer (pH 7.4) in total volume of 80 µL Measurements are obtained after a 1 hour incubation of the fluorescent ligand and the protein at 25°C with Safire 2 microplate reader. In a competition-binding assay, fluorescent ligand concentration is ≤2Kd, and protein concentration is set at which 50-80% of fluorescent ligand is bound. Dissociation constant of a competing ligand is calculated with the correction to Cheng-Prussoff equation introduced by Nicolovska-Coleska and colleagues. Assuming one-site competitive binding model, the equation used to calculate Ki’s from IC50 values

    Cell Assay: Murine macrophage RAW264.7 cells are plated at a density of 1×104 cells per well in a 96-well plate and incubated at 37°C for 18 h. The cells are then treated with the diazobenzene bromodomain inhibitors (e.g., MS436) up to 100 µM for 24 hours. At the end of the 24 hr incubation, 10 µL of the MTT solution (4 mg/mL) is added to each well and incubated at 37°C for 4 h. The supernatants are then removed and the cells are solubilized in 100 µL of 100% DMSO. The diazobenzene compounds are first dissolved in DMSO then diluted with culture medium to concentrations that ranged from 0.28 to 50000 nM. The final concentration of DMSO is adjusted to 0.05% (v/v). The extent of the reduction is measured by the absorbance at 570/630 nm using EnVison 2104 Multilabel Reader

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    J Med Chem. 2013 Nov 27;56(22):9251-64.

    These protocols are for reference only. InvivoChem does not independently validate these methods.


    Characterization of effects of the diazobenzene BrD inhibitors on BRD4 function in gene transcription. J Med Chem. 2013 Nov 27; 56(22): 9251–9264.


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