TABLE 1

Cathepsin C inhibitor potencies (IC50) on recombinant enzyme, cell-based neutrophil elastase activation, and active site occupancy in EcoM-G cells

EcoM-G cells were differentiated for 24 h before addition of inhibitors to the cell culture media. The cells were harvested 24 h later and processed either for NE activity or cathepsin C EOA, as described in Materials and Methods. S.E.M. are indicated for all compounds tested in at least three independent assays. The average IC50 for each compound was calculated by averaging single IC50 values obtained in individual experiments.


Compound

Enzyme Potency Cathepsin C

Cell-Based Potency

Ratio NE Act/EOA
Cathepsin C EOA
NE Activation
nM μM
1 14 ± 1a 0.023 ± 0.011 0.16 ± 0.03a 7.0
2 10 ± 2 0.026 ± 0.006 0.15 ± 0.03 5.8
3 347 ± 72 2.23 ± 0.80 5.49 ± 1.17 2.5
4 793 ± 160 3.05 8.20 ± 0.75 2.7
5 986 ± 82 3.70 12.62 ± 2.68 3.4
6 11 ± 3 0.05 0.12 ± 0.02 2.2
7
722 ± 130
7.20
18.0 (n = 2)
2.5
  • a Value previously reported in Méthot et al. (2007).