TLR8 agonist 2 hydrochloride is a highly potent and selective agonist for human TLR8, with an EC50 of 3 nM, but demonstrates significantly weaker activity towards human TLR7 (EC50 of 33.33 μM).

TLR8:3 nM (EC50), TLR7:33.33 μM (EC50)

TLR8 agonist 2 (Example 1) elevates TNF-α, IL-12p40, IFN-γ, and IFN-α levels in human peripheral blood mononuclear cells (hPBMC) with EC50 values of 105 nM, 26 nM, 29 nM, and 2800 nM, respectively[1].

The pharmacokinetic parameters of TLR8 agonist 2 (Example 1) in mice administered intravenously at 1 mg/kg and orally at 5 mg/kg were evaluated. The T 1/2 of TLR8 agonist 2 were 0.25 h (1 mg/kg i.v.) and 0.5 h (5 mg/kg p.o.), with AUC last values of 450 ng/mL*hr (i.v.) and 624 ng/mL*hr (p.o.). The oral bioavailability (%F) was 27.7%[1].