Figure 3.

NF-κB-targeted therapeutics in inflammatory diseases. NF-κB signaling plays a pathogenic role in various inflammatory diseases; therefore, there are many therapeutic strategies for inflammatory diseases aimed at blocking NF-κB activity. First, inhibition of IKK kinase activity. Drugs such as aspirin and salicylate have the ability to specifically inhibit IKK, thereby preventing phosphorylation of IκBα. Second, inhibition of protease activity. Drugs such as PS-341 and lactacystin specifically inhibit 26S proteasome complex, thereby preventing IκBα degradation. Third, inhibition of nuclear translocation. Drugs such as tacrolimus and IκBα super-repressor specifically prevent NF-κB subunits RelA, p50, c-Rel and other members from entering the nucleus. Finally, inhibition of DNA binding. Drugs such as glucocorticoids and PPAR agonists have the ability to prevent NF-κB subunits from binging with target genes, and therefore inhibit the transcription.