Table 3. Protease Selectivity Profiling for 10d and (S)-17b.
| % inhibitiona |
% inhibitiona |
||||
|---|---|---|---|---|---|
| enzyme | 10d | (S)-17b | enzyme | 10d | (S)-17b |
| ACE | 7 | 0 | cathepsin-S | 12 | 2 |
| ACE2 | 1 | 0 | factor-XA | 3 | 0 |
| ADAM10 | 0 | 0 | furin | 0 | 0 |
| BACE-1 | 1 | 0 | IDE | 0 | 0 |
| caspase-1 | 1 | 0 | MMP-3 (stromelysin) | 13 | 63 (IC50 = 4.4 μM)b |
| caspase-2 | 0 | 0 | MMP-7 (matrilysin) | 7 | 4 |
| caspase-3 | 0 | 0 | MMP-12 | 40 (IC50 = 467 nM)b | 81 (IC50 = 1.8 μM)b |
| caspase-5 | 0 | 0 | MMP-13 | 97 | 97 |
| caspase-6 | 0 | 0 | neprilysin | 3 | −6 |
| caspase-7 | 1 | 8 | TACE | 4 | −3 |
| cathepsin-D | 3 | 0 | thrombin | −3 | −8 |
| cathepsin-K | 0 | 2 | uPA | 3 | 1 |
| cathepsin-L | 9 | 7 | |||
a
Percent inhibition was determined by using single-stranded peptide substrates at an inhibitor concentration of 1 μM. Assays were performed in duplicates, % inhibition was determined, and average values are present.
b
Additional specificity assays against MMP-3 and MMP-12 were performed to determine the IC50 values.