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AT791 is a potent and orally bioavailable TLR7 and TLR9 inhibitor. AT791 inhibits TLR7 and 9 signaling in a variety of human and mouse cell types and inhibits DNA-TLR9 interaction in vitro.

AT791 potently suppresses DNA stimulation of HEK:TLR9 cells, with IC₅₀ of 0.04 μM and is significantly less effective at suppressing R848 stimulation of HEK:TLR7 cells (IC₅₀= 3.33 μM) .
AT7916 suppresses TLR9-DNA interaction in vitro, with an IC₅₀ in the 1 to10 μM range.
AT791 and E6446 are typical of “lysosomotropic”compounds in that they are lipophilic and contain weak base amines. At neutral pH, such compounds are nonpolar and can penetrate lipid membranes, but within low pH vesicles they become protonated and are trapped (de Duve et al., 1974). Capillary electrophoresis showed that AT791 has pK_as of 7.9 and 6.1, and E6446 has pK_as of 8.6 and 6.5, indicating they would be more highly protonated in endolysosomal compartments compared with cytoplasm.

Short-term induction of serum interleukin-6 in mice by CpG1668 DNA is effectively suppresses by pretreatment with AT791 (20 mg/kg; p.o.).

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