BAY-678

Potent and selective HNE inhibitor. Activity in cellular assays not reported but no cell penetration issues are expected. Good bioavailability in rat with half-life of 1.3 h with PO administration. NB: this compound is much weaker against mouse/rat neutrophil elastase (Ki = 700/600 nM) compared to human NE (15 nM). This limits use in cell and, especially, in vivo models to those with human enzyme. One exception is rodent in vivo models where human NE is administered in the course of the experiment, for example as detailed in the paper. BAY 85-8501, described in the same publication, looks like a better tool and is significantly more potent (Ki = 0.080 nM for HNE and 6.0/8.0 nM for MNE/RNE). When tested in vivo for murine NE activity, the effect was seen only in some assay arms at about 1 mg/kg. It should be expected that much weaker BAY-678 will be inactive in rodent in vivo models unless the experimental setup involves administration of human NE.