TLR7/TLR8 modulator 31 is a potent, orally active, dual TLR7 and 8 agonist with LEC values of 0.15 and 0.16 uM, respectively.
TLR7/TLR8 modulator 31 displays a good off-target profile (Aa1A, D1, 5HT2A IC50>10 µM; CYP 2D6 IC50=5.7 µM), also shows no significant activity against a panel of 80 receptors.
TLR7/TLR8 modulator 31 induces IFNα and pro-inflammatory cytokines at low dose in vivo, inhibits HBV replication indirectly, via cytokine induction and immune cells activation.
TLR7/TLR8 modulator 31 induces endogenous IFNα, an interferon stimulated gene response (ISGs), and also activation of myeloid dendritic cells and monocytes towards a TH1 phenotype in both mice and cynomolgus monkeys in vivo.
