BMA097 is a small molecule STAT3 inhibitor with IC50 of 1.8 uM in STAT3-dependent luciferase assays, binds directly to the SH2 domain of STAT3 and specifically inhibits STAT3 Tyr705 phosphorylation and activation.
BMA097 inhibited the expression of STAT3 target genes, cyclin D1 and Bcl-xL.
BMA097 suppresses Tyr705 phosphorylation and activation of STAT3, but not the phosphorylation of Ser727, also has little effect on the level of total STAT3.
BMA097 treatment reduced IL-6-induced phosphorylation and activation of STAT3 in serum-starved MDA-MB-231 cells.
BMA097 inhibits STAT3 activation (phosphorylation and dimerization) and translocation into nucleus.
BMA097 does not inhibit STAT3 upstream kinase JAK2.
BMA097 inhibits survival and induces apoptosis of breast cancer cells, with IC50 of 0.9, 1.8, and 3.9 μM, respectively for MDA-MB-231, MDA-MB-468, and MCF7 (72 h).
BMA097 (10 and 40 mg/kg) suppresses growth of xenograft tumors and STAT3 activation in vivo.