Pharmacokinetic profile of A-740003 in rats: 5 μmol/kg i.v., i.p., and p.o

Human THP-1 cells differentiated with LPS and IFN-γ into a macrophage phenotype express P2X7 receptors and receptor activation lead to IL-1β release as well as Yo-Pro uptake. A-740003 potently blocked Yo-Pro uptake in differentiated human THP-1 cells (IC50 of 92 nM). A-740003 also blocked IL-1β release in the THP-1 cells (IC50 of 156 nM). A-740003, at concentrations up to 100 μM, did not significantly reduce agonist-evoked changes in intracellular calcium concentrations mediated by a variety of other P2X and P2Y receptors. A-740003 was also evaluated for its ability to interact with a large array of G-protein-coupled receptors, enzymes, transporters, and ion channels. A-740003 showed weak or no activity in all of these assays (IC50 > 5 μM).