SNT-8370 is a potent, selective and irreversible dual inhibitor targeting vascular adhesion protein-1 (VAP-1) and myeloperoxidase (MPO) with IC50 of 10 nM and 17 nM respectively.
SNT-8370 inhibited MPO-catalysed H2O2 consumption with IC50 of 0.08 uM, more significantly when compared to verdiperstat or PF06282999.
SNT-8370 also more efficiently inhibited MPO-catalysed HOCl production with IC50 of 0.25 uM, compared to verdiperstat or PF06282999.
SNT-8370 more potently inhibited MPO-mediated LDL lipid peroxidation (Fig. 3F), exhibiting an IC50 of 20 nM, 30-fold lower than the corresponding IC50 value for verdiperstat of 0.6 μM.
SNT-8370 exhibited a selectivity index of >100-fold over a panel of amine oxidase family, such as the monoamine oxidases, lysyl oxidases (LOX) and diamine oxidase (DAO).
SNT-8370 is metabolically stable, exhibits a favourable pharmacokinetic/pharmacodynamic profile without CNS penetration, and effectively inhibits VAP-1 and MPO activities.
SNT-8370 effectively inhibits leukocyte infiltration in mouse peritonitis, carrageenan air pouch, and lipopolysaccharide-induced lung injury models of acute inflammation.
SNT-8370 is also protective in preclinical models of myocardial ischemia-reperfusion injury and unilateral-ureteral-obstruction-induced nephropathy.