WZ-2-033 is a potent, selective STAT3 inhibitor, binds to the SH2 domain of the STAT3 protein with KD of 7.4 uM, disrupts STAT3 dimerization and significantly inhibits STAT3 signaling.
WZ-2-033 preferentially suppresses STAT3-DNA binding, with no obvious effect on STAT5-DNA-binding activity.
WZ-2-033 suppresses STAT3-dependent transcriptional activation, reduces tyrosine (Y705) phosphorylation level of STAT3 in HEK-293T cells, inhibits the expression of STAT3 downstream genes, including Bcl-2, Bcl-xL, and c-Myc, in TNBC and GC cells.
WZ-2-033 strongly suppresses the proliferation, colony survival, migration, and invasion of TNBC and GC cells with aberrantly active STAT3.
WZ-2-033 (5 or 15 mg/kg, i.p. per day) inhibits tumor growth in MGC-803 xenograft mice, significantly suppresses the level of pY705-STAT3 and subsequently downregulated the expression of STAT3-targeted genes in human TNBC cell xenografts.