STAT3-IN-9, a potent inhibitor of STAT3 activation at Tyr705, exhibits no impact on the phosphorylation of STAT1 at Tyr 701. Additionally, this compound efficiently induces apoptosis and cell cycle arrest specifically at the G2/M phase [1].

STAT3-IN-9 (compound C6) exhibited potent anti-tumor activity in vitro, with IC50 values of 0.16, 5.80, 1.63, 5.73, >25, and >25 μM against MDA-MB-468, MDA-MB-231, HepG2, A549, U251, and HCT116 cells, respectively, after 48 hours. At concentrations of 0, 0.2, 1.0, and 5.0 μM over 24 hours, STAT3-IN-9 selectively inhibited STAT3 (Tyr705) activation without affecting STAT1 (Tyr701) phosphorylation, induced apoptosis through the mitochondrial Caspase-dependent pathway, and caused cell cycle arrest at the G2/M phase in a dose-dependent manner. These findings highlight STAT3-IN-9’s targeted action in inhibiting tumor cell proliferation and promoting apoptosis without interfering with STAT1 activation.