Santonin-related compound 2 inhibits the nuclear translocation of NF-κB subunit p65 by targeting cysteine 38 in TNF-α-induced NF-κB signaling pathway.

(11S)-2α-Bromo-3-oxoeudesmano-12,6α-lactone, designated santonin-related compound 2 (SRC2), only weakly affected IκBα degradation after tumor necrosis factor-α (TNF-α) stimulation, but strongly blocked the nuclear translocation of nuclear factor κB (NF-κB) subunit p65. Replacement of Cys-38 of p65 with serine abolished the inhibitory effect of SRC2 on this TNF-α-induced nuclear translocation. These results indicate that SRC2 inhibits the nuclear translocation of p65 by targeting Cys-38.