Human tumour necrosis factor alpha (TNF-α) promoter contains motifs that resemble NF-κB -binding sites. It has been suggested that NF-κB is an important factor in lipopolysaccharide (LPS)-induced TNF-α production1^ NF-κB normally resides in cytoplasm as an inactivated form by forming a complex with IκB-α. Upon LPS stimulation, IκB-α is rapidly phosphorylated by IκB kinase 2 (IKK2) and degraded, allowing NF-κB to translocate to the nucleus, where it participates in transcriptional regulation of target genes such as TNF-α2). NF-κB signaling pathway is thought to be the target for antiinflammatory agents because it activates various gene expression involved in inflammation. In addition, increasing evidence supports its role in regulating cell growth, oncogenesis and protection from cell death3). We screened inhibitors of LPS-induced TNF-α production with a reporter assay system and found NK30424A and B which have ability to suppress LPS induced TNF-α production below 1μM, from the fermentation broth of Streptomyces sp. NA30424. NK30424A was a unique glutarimide compound having an unsaturated 12-membered lactone containing cysteine moiety, and NK30424B was a stereoisomer of A (Fig. 1). We expect that NK30424A and B inhibit LPS-induced TNF-α production by suppression of NF-κB signaling pathway, and have potential for treatment of this pathway mediated pathophysiological diseases. In this communication, we report our screening strategy, taxonomy of the strain NA30424, production, structure and biological activities of NK30424A and B.