A novel inhibitor of STAT6 activation, named as TMC-264 (1), was discovered from the fermentation broth of Phoma sp. TC 1674. Based on spectroscopic analyses, TMC-264 was found to be a novel tricyclic polyketide with chloro-1H-dibenzo[b, d]pyran-4, 6-dione. TMC-264 suppressed expression of IL-4 driven luciferase and germline Cε mRNA with IC₅₀ values of 0.3μM and 0.4μM, respectively. TMC-264 exhibited a potent inhibitory activity against tyrosine phosphorylation of STAT6 with an IC₅₀ value of 1.6μM, whereas TMC-264 weakly inhibited tyrosine phosphorylation of STAT5 with an IC₅₀ value of 16μM, but did not inhibit the phosphorylation of STAT1 up to 40μM. TMC-264 blocked formation of the complexes between phosphorylated STAT6 and STAT6 oligonucleotides in a dose dependent manner, while TMC-264 did not affect the formation of phosphorylated STAT1/STAT1 oligonucleotides complexes. These results suggested that TMC-264 selectively inhibited IL-4 signaling by interfering both of phosphorylation of STAT6 and binding of the phosphorylated STAT6 to the recognition sequence.