SH-4-54

A potent, BBB permeable, nonphosphorylated STAT3 inhibitor that strongly binds to STAT3 protein with Kd of 300 nM; potently kills glioblastoma brain cancer stem cells (BTSCs) and effectively suppresses STAT3 phosphorylation and its downstream transcriptional targets at low nM concentrations; potently suppresses glioma tumor growth, and inhibits pSTAT3 in vivo.(In Vitro):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 shows unprecedented cytotoxicity in human BTSCs, displays no toxicity in human fetal astrocytes, potently suppresses pSTAT3 with nanomolar IC50s, inhibiting STAT3's downstream targets, and shows no discernible off-target effects at therapeutic doses.(In Vivo):SH-4-54 exhibits blood-brain barrier permeability potently controls glioma tumor growth, and inhibits pSTAT3 in vivo. SH-4-54 demonstrates the power of STAT3 inhibitors for the treatment of BTSCs and validates the therapeutic efficacy of a STAT3 inhibitor for GBM clinical application.SH-4-54 decreases pSTAT3 expression in tumor cells of treated mice. SH-4-54 appears to decrease proliferation and increase apoptosis of treated tumors.