SH-4-54

1456632-40-8

C29H27F5N2O5S

DMSO : 100 mg/mL (163.78 mM; Need ultrasonic); H2O : < 0.1 mg/mL (insoluble)

JAK/STAT Signaling; Stem Cell/Wnt

SH-4-54 is a most potent, small molecule, nonphosphorylated STAT inhibitor, with K_Ds of 300, 464 nM for STAT3 and STAT5, respectively. IC50 & Target: KD: 300 nM (STAT3), 464 nM (STAT5)^[1]. 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^[1]. 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^[1].