SH-4-54 strongly binds to STAT3 protein (K D = 300 nM). SH-4-54 potently kills glioblastoma brain cancer stem cells (BTSCs) and effectively suppresses STAT3 phosphorylation and its downstream transcriptional targets at low nM concentrations. SH-4-54 exhibites blood-brain barrier permeability, potently controlled glioma tumor growth, and inhibites pSTAT3 in vivo.
|Source||Int J Mol Sci (2018). Figure 4. SH-4-54|
|Method||cell viability assay|
|Cell Lines||LX-2 and HSC-T6|
|Concentrations||1.5 μM or 0.5 μM|
|Incubation Time||48 h|
|Results||A second STAT3 specific inhibitor, SH-4-54, inhibited LX-2 cell viability in a dose-dependent manner with an IC50 of 0.37 μM.|
|Cell lines||BTSC lines 25M, 67EF, 73EF, 84EF and 127EF|
|Preparation method||Dissociating BTSC spheres to single cells with the enzyme Accumax, seeding at 1500 cells/ 96-well and treating with drug or vehicle (DMSO) one day after plating. Repeating cytotoxicity studies independently using BTSC lines 25M, 67EF, 73EF, 84EF and 127EF.Dissociating BTSC spheres to single cells as above and plating in 96 well plates in triplicate at 3000 cells/ 96-well. In both sets of experiments using drugs as serial dilutions within the range of 5 μM to 100 nM in the first set and 25 μM to 10 nM. Assessing cell viability following drug treatment three days later using the alamarBlue assay according to the manufacturer’s instructions. All culture experiments are performed in triplicate with a minimum of three wells per condition|
|Incubation time||72 hours|
|Animal models||NOD-SCID bearing ed with BT73 glioma xenografts|
|Dosages||Suspended in 50% polyethylene glycol 300 in water|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
Potent Targeting of the STAT3 Protein in Brain Cancer Stem Cells: A Promising Route for Treating Glioblastoma.
Haftchenary S, et al. ACS Med Chem Lett. 2013 Sep 8;4(11):1102-7. PMID: 24900612.
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