Bt354 is a specific, small-molecule inhibitor of the STAT3 signalling pathway, prevents STAT3 from entering the nucleus and phosphorylates it at Y705, exhibiting potent anticancer properties.
Bt354 also is a potent and orally active tubulin inhibitor, inhibited tubulin polymerization, promoted mitotic blockade and apoptosis, and exhibited significant antiproliferative activities against various cancer cell lines (DU145, IC50= 8 nM).
Bt354 inhibits phosphorylation of STAT3 at Y705, without affecting the phosphorylation of STAT3 at S727 in breast cancer cells.
Bt354 inhibited the nuclear translocation of STAT3 and consequently induced cell growth inhibition, apoptosis and cell cycle G2/M arrest in triple negative breast cancer cells.
Bt354 also inhibited tumour growth in MDA-MB-435 and MDA-MB-231 xenograft mice without affecting body weight.
Bt354 significantly reduced CCI-induced mechanical allodynia and thermal hyperalgesia, accompanied by a marked decrease in phosphorylated STAT3 (pSTAT3) expression in spinal neurons.
Bt354 attenuated the polarization of M1-type microglia and A1-type astrocytes, suppressed inflammasome-related signaling, and mitigated neuroinflammatory responses.
Bt354 inhibited the nuclear translocation of neuronal pSTAT3, which is a critical step in regulating pro-inflammatory gene transcription.