Microbial and plant secondary metabolites are the treasury of useful chemotherapeutic compounds, enzyme inhibitors, and other bioactive compounds. We initiated the screening of signal transduction inhibitors of small molecular weight in 1990s. NF-κB is the transcription factor that promotes transcription of inflammatory cytokines, cell adhesion molecules, and inhibitor of apoptosis proteins. Therefore, inhibitors of NF-κB function should be useful as anti-inflammatory and anticancer agents. They should be also useful to study the role of NF-κB in various biological phenomena. We have designed a new NF-κB inhibitor, DHMEQ, based on the structure of epoxyquinomicin isolated from Amicolatopsis. DHMEQ was shown to inhibit NF-κB activity at the level of nuclear translocation. Cell adhesion to the endothelial cells would be involved in the etiology of atherosclerosis and blood-borne metastasis. DHMEQ inhibited the expression of adhesion molecules in endothelial cells. It is likely that macrophages play important roles in induction of inflammation and progression of tumors. DHMEQ inhibited the production of nitrogen oxide, the secretion of inflammatory cytokines such as IL-1β, IL-6, IL-12, and TNF-α, and the phagocytotic activity in macrophages. It suppressed rheumatoid anthritis and prostate carcinoma in mice. Thus, NF-κB was shown to play important roles in cell adhesion to endothelial cells, activation of macrophages, and progression of tumors. Since DHMEQ shows very little toxicity in mice, it is being developed as an anticancer agent. [Jpn J Physiol 54 Suppl:S14 (2004)]