STAT3-IN-27 (Compound 41) is an orally active STAT3 inhibitor that impedes STAT3 phosphorylation with a KD of 4.4 μM and suppresses STAT3 transcriptional activity with an IC50 of 22.57 nM. It inhibits the proliferation of various cancer cells with an IC50 ranging from 10 to 500 nM. STAT3-IN-27 causes cell cycle arrest at the G2/M phase, induces mitochondrial dysfunction and apoptosis in HCT116 cells, and inhibits HCT116 cell migration. It exhibits antitumor effects in mouse models.