TLR7 agonist 1 is a selective TLR7 agonist with an LEC value of 90 nM. TLR7 agonist 1 activates downstream immune regulation and shows no activity against TLR8. TLR7 agonist 1 induces endogenous IFN-α production in mice [1].
In Vivo, TLR7 agonist 1 (compound 48) (5 mg/kg; p.o.; single dose) induces a peak plasma mIFN-α level of 2800 pg/mL at 4 hours in healthy C57BL/6 mice, with higher liver exposure than systemic exposure[1].
In Vitro, TLR7 agonist 1 (compound 48) (0.09 μM) is a highly potent, TLR7-selective agonist (SI >200 over TLR8) in HEK-293 cells transiently transfected with human TLR7, with an hTLR7 LEC of 0.09 μM[1]. TLR7 agonist 1 (0.14 μM) induces IFN-α in hPBMCs with an LEC50 of 0.14 μM[1]. TLR7 agonist 1 (>25 μM) has low cytotoxicity in HEK-293 cells[1]. TLR7 agonist 1 (1 μM; 15 min) exhibits moderate metabolic stability in human liver microsomes[1]. TLR7 agonist 1 (10 μM) shows no CYP inhibition up to 10 μM in human liver microsomes[1].
References:
[1]. Pieters S, et al. Discovery of selective 2,4-diaminoquinazoline toll-like receptor 7 (TLR 7) agonists. Bioorg Med Chem Lett. 2018;28(4):711-719.
In Vivo, TLR7 agonist 1 (compound 48) (5 mg/kg; p.o.; single dose) induces a peak plasma mIFN-α level of 2800 pg/mL at 4 hours in healthy C57BL/6 mice, with higher liver exposure than systemic exposure[1].
In Vitro, TLR7 agonist 1 (compound 48) (0.09 μM) is a highly potent, TLR7-selective agonist (SI >200 over TLR8) in HEK-293 cells transiently transfected with human TLR7, with an hTLR7 LEC of 0.09 μM[1]. TLR7 agonist 1 (0.14 μM) induces IFN-α in hPBMCs with an LEC50 of 0.14 μM[1]. TLR7 agonist 1 (>25 μM) has low cytotoxicity in HEK-293 cells[1]. TLR7 agonist 1 (1 μM; 15 min) exhibits moderate metabolic stability in human liver microsomes[1]. TLR7 agonist 1 (10 μM) shows no CYP inhibition up to 10 μM in human liver microsomes[1].
References:
[1]. Pieters S, et al. Discovery of selective 2,4-diaminoquinazoline toll-like receptor 7 (TLR 7) agonists. Bioorg Med Chem Lett. 2018;28(4):711-719.