MPO inhibitor IN-4 is a highly potent, selective, irreversible and orally bioavailable myeloperoxidase (MPO) inhibitor.
IN-4 is selective for extracellular MPO over intracellular (neutrophil) MPO, displays significant selectivity over the closely related thyroid peroxidase (TPO).
IN-4 displays similar in vitro potency across peroxidation, plasma and NETosis assays (IC50=80-177 nM).
IN-4 shows good exposure, low clearance and high oral bioavailability in mice, rats and dogs.
IN-4 (25-250 mg/kg/day, oral) exhibited a dose-dependent inhibition of MPO activity in three mouse models of inflammation.
