Interleukin-4 (IL-4) signal transduction via IL-4 receptor, Janus kinase 1 and 3 (JAK1 and JAK3), and signal transducer and activator of transcription 6 (STAT6) are essential for the production of IgE. IL-4 receptor associated JAKI and JAK3 phosphorylate a tyrosine residue 641Tyr of STAT6 after IL-4 stimulation. The phosphorylated STAT6 forms a homodimer, translocates to the nucleus, and binds to the STAT6 recognition sequences (TTCCCAAGAA) within the promoter region of germline Cε1,2). Expression of germline Cε mRNA plays a critical role in the immumogloblin isotype switching from IgM to IgE in B cells3,4). IgE induces release of inflammatory mediators in mast cells to cause allergic diseases such as asthma, nasal inflammation and atopic dermatitis. Thus, the IL-4 signal transduction might be a therapeutic target for allergic diseases. As a result of screening for inhibitors of IL-4 signal transduction using an IL-4 driven luciferase assay system, we found new naphtho-γ-pyrones (TMC-256A1 and C1) and a novel tricyclic polyketide (TMC-264) from the fermentation broth of Aspergillus niger var. niger TC 16295) and Phoma sp. TC 16746,7), respectively. Further screening identified a new inhibitor of IL-4 signal transduction designated as TMC-260 (Fig. 1) from the fermentation broth of Acremonium kiliense Grutz TC 1703. This report describes the taxonomy, fermentation, isolation, structure determination and biological activities of TMC-260.