ETI60 (endosomal TLR inhibitor 60) is a potent, selective inhibitor of endosomal Toll-like receptors (TLR3, TLR7, TLR8 and TLR9) with IC50 of 20-3 00 nM for TLR3, TLR7 and TLR9, and 2 uM for TLR8.
ETI60 effectively suppresses the secretion of pro-inflammatory cytokines mediated by endosomal TLR3, TLR7, TLR8 and TLR9 in various cell types, including RAW 264.7 macrophages, human Daudi cells and THP-1 monocytes, as well as in primary murine BMDCs.
ETI60 does not inhibits any plasma membrane TLR, including TLR1/TLR2, TLR2/TLR6, TLR4 and TLR5, in differentiated human THP-1 cells activated by FSL-1, Pam3CSK4, LPS and FLA-ST, respectively.
ETI60 (10 uM) inhibits IMQ- or ODN2395-induced phosphorylation of MAPKs (p-ERK, p-JNK and p-p38), nuclear translocation of the NF-κB p65 subunit, Iκ-Bα degradation and IRF7 expression in RAW 264.7 cells.
ETI60 ameliorated IMQ-induced autoimmune diseases by suppressing the expression of inflammation-associated genes.
ETI60 (60 mg/kg, daily, oral) ameliorate IMQ- and IL-23-induced psoriasis in mice.
ETI60 (30 mpk) in the MRL/lpr female mouse model of SLE.