BAY-85-8501 is a selective, reversible, and potent inhibitor of Human Neutrophil Elastase (HNE) with an IC50 of 65 pM.

HNE:65 pM

In this study, the exogenous compound HNE noxa is identified as the primary cause of lung injury and hemorrhage. BAY-85-8501 (29), due to its picomolar potency against HNE and high effectiveness against MNE, completely prevents lung injury and subsequent inflammation if administered one hour before exposure to HNE noxa. Despite its high selectivity for HNE inhibition, BAY-85-8501 does not prevent primary lung injury caused by PPE since it has no effect on it. However, BAY-85-8501 can inhibit MNE, an endogenous promoter of inflammation and secondary lung injury, albeit with lower potency. The prevention of inflammation and secondary injury by BAY-85-8501 is less pronounced and requires doses 30 times higher than standard. Its effectiveness primarily relies on its ability to inhibit MNE (Ki=6 nM) in these cases. At a dosage of 0.01 mg/kg, a significant reduction in hemoglobin concentration is noted, and at 0.1 mg/kg, a notable decrease in neutrophil count is observed, indicating efficacy is largely dependent on its potency against HNE (Ki=0.08 nM) in this scenario.