Figure 1: Chemical structures of serine elastase inhibitors (SEI), CE-2072 and AI-158.Both CE-2072 and AI-158 are potent inhibitors of neutrophil elastase (NE) and proteinase-3 (PR3) (Table 1). Importantly, for our studies, since both enzymes are stored in an active state and bound to proteoglycans in the azurophilic granules of neutrophils and monocytes/macrophages, both drugs have been demonstrated to penetrate intracellularly and inhibit their target enzymes [>90% inhibition] at concentrations exceeding 0.3 μM (data not shown). Neither compound has any inhibitory activity against other serine proteinases, such as cathepsin G, trypsin, chymotrypsin, thrombin, plasmin, human tissue plasminogen activator, nor any of the clotting factors at concentrations over 100-fold higher than those used in our studies. Similarly, these compounds had no inhibitory activity, at any concentration, against representative aspartyl-, cysteine- or metallo-proteinases