SH-4-54

• CAT Number: I001762
• CAS Number: 1456632-40-8
• Molecular Formula: C29H27F5N2O5S
• Molecular Weight: 610.59
• Purity: ≥95%
• Target: STAT3
• Solubility: 10 mM in DMSO
• Storage: room temp
• IC50: 300 nM (KD, for STAT3)
• InChI: InChI=1S/C29H27F5N2O5S/c1-35(42(40,41)28-26(33)24(31)23(30)25(32)27(28)34)16-22(37)36(21-13-11-20(12-14-21)29(38)39)15-17-7-9-19(10-8-17)18-5-3-2-4-6-18/h7-14,18H,2-6,15-16H2,1H3,(H,38,39)
• InChIKey: VFPYGNNOSJWBHF-UHFFFAOYSA-N
• SMILES: O=C(O)C1=CC=C(N(CC2=CC=C(C3CCCCC3)C=C2)C(CN(C)S(=O)(C4=C(F)C(F)=C(F)C(F)=C4F)=O)=O)C=C1

SH-4-54 is a most potent, small molecule, nonphosphorylated STAT3 inhibitor, strongly binds to STAT3 protein (KD = 300 nM), is selective for STAT3 over STAT1.IC50 value: 300 nM (KD, for STAT3)Target: STAT3in 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, displayed no toxicity in human fetal astrocytes, potently suppressed pSTAT3 with nanomolar IC50s, inhibited STAT3/’s downstream targets, and showed no discernible off-target effects at therapeutic doses.in vivo: SH-4-54 exhibits blood-brain barrier permeability, potently controlled glioma tumor growth, and inhibited 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.

Reference

[1]. Haftchenary S, et al. Potent Targeting of the STAT3 Protein in Brain Cancer Stem Cells: A Promising Route for Treating Glioblastoma. ACS Med Chem Lett. 2013 Sep 8;4(11):1102-1107.