STAT3 inhibitor YZ-35 is potent, selective STAT3 inhibitor with binding Kd of 190 nM in ITC assays amd Ki of 380 nM in FP assays.
YZ-35 directly binding to the SH2 domain.
YZ-35 demonstratessuperior inhibitory potency (IC50 = 0.63 μM) against MDA-MB-231 cells compared to juglone, Stattic, and TTI-101.
YZ-35 exhibits concentration- and time-dependent suppression of the phosphorylation of STAT3 at both Tyr705 and Ser727 residues in MDA-MB-231 and MCF-7 cell lines, while maintaining total STAT3 protein levels。
YZ-35 does not affect expression levels of STAT1 and STAT5 or inhibits their phosphorylation, also has no impact the phosphorylation of JAK2, Src, and ERK.
YZ-35 inhibits the expression of critical apoptosis-related proteins, including Cyclin D1, BCL-2, BCL-xL, and Survivin.
YZ-35 significantly inhibits the proliferation, migration, and promoted apoptosis of BRCA cells.
YZ-35 reduces tumor stemness in BRCA.
YZ-35 (5-10 mg/kg, i.v.) inhibits BRCA development on the xenograft model.