One approach for inhibiting NF-κB activation is to use small peptides that cross the cell membrane and block the nuclear translocation of the NF-κB complex [101–103]. For example, SN50, a forty-one-residue synthetic peptide that contains a hydrophobic membrane-translocating region and the nuclear localization sequence of NF-κB p50 [101], can enter cells and compete with NF-κB complexes for the machinery responsible for the nuclear translocation of NF-κB. SN50 effectively inhibits the LPS- and TNF-α-induced nuclear translocation of NF-κB in different cell lines [101, 104–107] and mitigates inflammatory responses in vivo [108, 109]. However, SN50 also blocks the nuclear translocation of a number of other transcription factors [102]. Dehydroxymethylepoxyquinomicin, a fungal epoxyquinoid that has anti-inflammatory and antitumor activity in several mouse models, has been reported to be a specific inhibitor of NF-κB nuclear translocation [110].
