W1131 is a potent and selective STAT3 inhibitor with Kd of 7.55 uM in surface plasmon resonance (SPR) assays, inhibits STAT3 Tyr705 phosphorylation, triggers ferroptosis and possesses potent anti-tumor effects both in vitro and in vivo.
W1131 inhibited STAT3 tyrosine phosphorylation and dimerization, accumulation of nuclear pY705-STAT3, and transcriptional activity.
W1131 inhibited STAT3 Tyr705 phosphorylation in a time- and dose-dependent manner without obvious effect on the activation of STAT1 and STAT5, W1131 had no obvious effect on phospho-JAK2 or phospho-AKT levels.
W1131 strongly inhibited cell survival, migration, and invasion, W1131 (1 uM) triggers ferroptosis and inhibited GPX4, SLC7A11, and FTH1 expression in gastric cancer cells.
W1131 (3 mg/kg and 10 mg/kg, i.p.) induced ferroptosis and regressed tumor growth of gastric cancer in vivo.
W1131 also alleviated chemotherapy resistance (5-FU) in multiple models of gastric cancer.