Molecular Weight(MW): 383.42
MS436 is a selective BET bromodomain inhibitor with Ki of <0.085 μM and 0.34 μM for BRD4 (1) and BRD4 (2), respectively.
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|Description||MS436 is a selective BET bromodomain inhibitor with Ki of <0.085 μM and 0.34 μM for BRD4 (1) and BRD4 (2), respectively.|
MS436 exhibits low nanomolar affinity with preference for the first bromodomain over the second. MS436 effectively inhibits BRD4 activity in NF-κB-directed production of nitric oxide and proinflammatory cytokine interleukin-6 in murine macrophages without siginificanty inhibition on cell viability. 
Fluorescence Anisotropy Binding Assay:Binding affinity of the newly synthesized diazobenzene compounds 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 was 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 recovered from fitting data using Prism.
|In vitro||DMSO||55 mg/mL (143.44 mM)|
|Ethanol||1 mg/mL warmed (2.6 mM)|
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