W1307 is a potent and highly selective STAT3 inhibitor with SPR KD of 1.74 uM, demonstrates significant anti-tumor activity both in vitro and in vivo.
W1307 binds to and stabilizes the STAT3 protein in AML cells in CETSA assays.
W1307 (0-3 uM) inhibits Tyr705 phosphorylation of STAT3 in a time-dependent manner in K562 and MOLM-13, suppresses the expression of its downstream targets (c-Myc, Mcl-1, and Bcl-2), without affecting STAT1/5 phosphorylation, nor phospho-AKT levels, the upstream kinase of STAT3.
W1307 disrupts STAT3-STAT3 dimerization in 293T cells for Co-IP analysis.
W1307 strongly suppresses AML cell proliferation, survival and induces apoptosis.
W1307 (5 or 15 mg/kg) exhibited significant, dose-dependent anti-leukemic effects in murine AML model by intravenously injecting MOLM-13-EGFP/Luc cells into NOD-SCID mice.
W1307 enhances the anti-tumor effect of Ara-C and sensitizes resistant AML cell line to Ara-C through disrupting lipid homeostasis and triggering lipotoxicity.