GSK2245035 is a toll-like receptor 7 (TLR7) agonist.1 It selectively induces the production of IFN-α over TNF-α in isolated human peripheral blood mononuclear cells (PBMCs; EC50s = 0.63 and 316 nM, respectively), as well as over the production of TNF-α, IL-1β, IFN-γ, IL-10, and IL-12p70 in isolated human whole blood (EC50s = 63-10,000 nM). GSK2245035 (0.1-1,000 nM) reduces timothy grass- or house dust mite-induced IL-10 and IL-5 release in isolated human PBMCs. Intranasal administration of GSK2245035 (0.03-1 mg/kg) increases serum IP-10 levels, a marker of IFN-α induction, in mice. It also increases serum levels of IP-10 in cynomolgus monkeys.
1.Biggadike, K., Ahmed, M., Ball, D.I., et al.Discovery of 6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[5-(1-piperidinyl)pentyl]-7,9-dihydro-8H-purin-8-one (GSK2245035), a highly potent and selective intranasal toll-like receptor 7 agonist for the treatment of asthmaJ. Med. Chem.59(5)1711-1726(2016)