STAT3-IN-32 (compound 4c) is an orally active, potent dual phosphorylation inhibitor of STAT3. It demonstrates significant inhibition of STAT3 luciferase activity in HEK293T cells, with an IC50 of 5.3 nM, and inhibits ATP production in BxPC-3 cells with an IC50 of 4.2 nM. By targeting the STAT3 SH2 domain (KD=21.3 nM), STAT3-IN-32 effectively blocks p-Tyr705 and p-Ser727, leading to the attenuation of STAT3 nuclear transcription and mitochondrial oxidative phosphorylation. Furthermore, this compound displays notable suppressive effects in a pancreatic cancer xenograft model.