Molecular Weight(MW): 610.59
SH-4-54 is a potent STAT inhibitor with KD of 300 nM and 464 nM for STAT3 and STAT5, respectively.
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|Description||SH-4-54 is a potent STAT inhibitor with KD of 300 nM and 464 nM for STAT3 and STAT5, respectively.|
SH-4-54 shows unprecedented cytotoxicity in human glioblastoma brain cancer stem cells (BTSCs), while has no toxicity in human fetal astrocytes. In addition, SH-4-54 effectively suppresses STAT3 phosphorylation and its downstream transcriptional targets. 
|In vivo||In mice orthotopically xenografted with BT73, SH-4-54 (10 mg/kg i.p.) exhibits BBB permeability, potently suppresses glioma tumor growth, and inhibits pSTAT3. |
Surface Plasmon Resonance (SPR) studies:The binding experiments are carried out on a ProteOn XPR36 biosensor at 25°C using the HTE sensor chip. The flow cells of the sensor chip are loaded with a nickel solution at 30 μL/min for 120 s to saturate the Tris–NTA surface with Ni(II) ions. Purified His-tagged STAT3 and STAT5 in PBST buffer (PBS with 0.005% (v/v) Tween-20 and 0.001% DMSO pH 7.4) is injected in the first and second channels of the chip respectively in the vertical direction at a flow rate of 25 μg/μL for 300 s, which attained, on average, ~8000 resonance unit (RU). After a wash with PBST buffer, inhibitors binding to the immobilized proteins is monitored by injecting a range of concentrations along with a blank at a flow rate of 100 μL/min for 200 s for each of these small molecules. When the injection of the small molecule inhibitor is completed, running buffer is allowed to flow over the immobilized substrates for the non-specifically bound inhibitors to dissociate for 600 s. Following dissociation of the inhibitors, the chip surface is regenerated with an injection of 1 M NaCl at a flow rate of 100 μL/ml for 18 s. Interspot channel reference is used for non-specific binding corrections and the blank channel used with each analyte injection served as a double reference to correct for possible baseline drift. Data are analyzed using ProteOn Manager Software version 3.1. The Langmuir 1:1 binding model was used to determine the KD values.
|In vitro||DMSO||100 mg/mL (163.77 mM)|
|Ethanol||50 mg/mL warmed (81.88 mM)|
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