Signal transducer and activator of transcription 3 (STAT3) is a cytokine-inducible transcription factor with roles in inflammation and cancer. ML115 is an isoxazole carboxamide that acts as a cell-permeable STAT3 activator (EC50 = 2 nM) and is more than 28,000-fold selective for STAT3 over STAT1 and NF-κB. It shows no cytotoxicity against HT-1080 or NIH-3T3 cells. ML115 increases the expression of BCL3, a known STAT3-dependent oncogene, and enhances STAT3 activation by the pro-inflammatory cytokine IL-6. As the maintenance of pluripotency in mouse embryonic stem cells requires continued activation of STAT3, ML115 may be useful in maintaining embryonic stem cells in an undifferentiated state.