Cell penetrating peptide inhibitors of Nuclear Factor-kappa B

The nuclear factor kappa B (NF-kappa B) transcription factors are activated by a range of stimuli including pro-inflammatory cytokines. Active NF-kappa B regulates the expression of genes involved in inflammation and cell survival and aberrant NF-kappa B activity plays pathological roles in certain types of cancer and diseases characterized by chronic inflammation. NF-kappa B signaling is an attractive target for the development of novel anti-inflammatory or anti-cancer drugs and we discuss here how the method of peptide transduction has been used to specifically target NF-kappa B. Peptide transduction relies on the ability of certain small cell-penetrating peptides (CPPs) to enter cells, and a panel of CPP-linked inhibitors (CPP-Is) has been developed to directly inhibit NF-kappa B signaling. Remarkably, several of these NF-kappa B-targeting CPP-Is are effective in vivo and therefore offer exciting potential in the clinical setting.