In a search for inhibitors of the inducible tumor necrosis factor-α (TNF-α) promoter activity and synthesis, a new chlorinated cyclopentenone was isolated from fermentations of the ascomycete Mollisia melaleuca. The structure was determined by a combination of spectroscopic techniques. The compound blocked the inducible human TNF-α promoter activity and synthesis with IC₅₀-values of 2.5-5 μg/ml (8.1-16.1 μм). Studies on the mode of action of the compound revealed that the inhibition of TNF-α promoter activity is caused by an inhibition of the phosphorylation of the IϰB protein which prevents the activation of the transcription factor NF-ϰB. No cytotoxic, antibacterial and antifungal activities could be observed up to 100 μg/ml (323 μм) of the compound.