IRF5 inhibitor N5-1 (PRRVRLK) is a cell permeable, IRF5 peptide mimetic that selectively bind to and stabilizes the inactive IRF5 monomer with KD of 98.8 nM.
IRF5 inhibitor N5-1 binds to endogenous IRF5, but not IRF3 or IRF7, in human primary monocytes.
IRF5 inhibitor N5-1 significantly reduced R848-induced IRF5 nuclear translocation in monocytes.
IRF5 inhibitor N5-1 binds to the C-terminal IAD of inactive IRF5 monomer and inhibits phosphorylation of Ser462, readily enters primary immune cells to inhibit R848-induced IRF5 nuclear translocation with low associated toxicity.
IRF5 inhibitor N5-1 is a potent inhibitor of TLR7-induced IRF5 nuclear translocation in monocytes and B cells, selectively inhibits IRF5-mediated inflammatory cytokine expression in PBMCs.
IRF5 inhibitor N5-1 attenuated IL-6 production and IRF5 hyperactivation in NZB/W F1 mice, and reducedkidney pathology and increased overall survival in NZB/W F1 mice from spontaneous onset of lupus and mortality.