AT791 is an effective TLR7 and TLR9 inhibitor with oral activity. AT791 has inhibitory effects on TLR7 and TLR9 signal transduction in various types of human and mouse cells. AT791 inhibits DNA-TLR9 interaction in vitro.

AT791 effectively inhibits DNA-induced activation of HEK:TLR9 cells, demonstrating a potent suppression with an IC 50 of 0.04 μM, whereas its suppression of R848-induced activation in HEK:TLR7 cells is notably less potent (IC 50 = 3.33 μM). Similarly, AT7916 blocks the interaction between TLR9 and DNA in vitro, achieving an IC 50 within the range of 1 to 10 μM. Both AT791 and E6446 exemplify the characteristics of lysosomotropic compounds, being lipophilic and containing weak base amines, which allow them to cross lipid membranes easily at a neutral pH. Inside low pH vesicles, these compounds become protonated and are retained. Through capillary electrophoresis, it has been identified that AT791 possesses pKa values of 7.9 and 6.1, whereas E6446 shows pKa values of 8.6 and 6.5. These results suggest that both compounds are more prone to protonation within endolysosomal compartments than in the cytoplasm, supporting their mechanism of action.

Pretreatment with AT791 (20 mg/kg; p.o.) [1] effectively suppresses the short-term induction of serum interleukin-6 in mice induced by CpG1668 DNA.