Inhibition Profile of Endothelial Cell Prekallikrein-Activating Enzyme(s)
| Inhibitor Class . | Inhibitor . | [Inhibitor]* . | % Inhibition† . | % Kallikrein Inhibition‡ . |
|---|---|---|---|---|
| Cysteine protease inhibitors | Antipain | 100 μmol/L | 92 ± 7.1 | ≤5% |
| Cysteine | 10 mmol/L | 99 ± 3.4 | ≤5% | |
| HgCl2 | 1 mmol/L | 96 ± 3.6 | ≤5% | |
| DTT | 10 mmol/L | 99 ± 3.5 | 28.6% | |
| 2-Mercaptoethanol | 5% | 98 ± 2.3 | ≤5% | |
| Glutathione | 100 μmol/L | 62 ± 4.5 | 10.4% | |
| Calpain Inhibitor | 10 mmol/L | 46 ± 3.6 | ≤5% | |
| Z-Phe-OH | 1 mmol/L | 45 ± 2.4 | ≤5% | |
| E64 | 10 mmol/L | 2.5 ± 3.8 | ≤5% | |
| Iodoacetamide | 10 mmol/L | 2.5 ± 1.5 | ≤5% | |
| Iodoacetic Acid | 10 mmol/L | 3.1 ± 1.8 | ≤5% | |
| N-ethylmalimide | 3 mmol/L | 0.3 ± 0.1 | Not done | |
| Cystatin | 1 mmol/L | 1.0 ± 0.3 | ≤5% | |
| OH-Mercuribenoic Acid | 10 mmol/L | 1.2 ± 0.1 | ≤5% | |
| Metalloprotease inhibitors | Zincov | 100 μmol/L | 20 ± 2.5 | ≤5% |
| TIMP-1 | 20 μg/mL | 15 ± 2.9 | ≤5% | |
| TIMP-2 | 20 μg/mL | 0.4 ± 0.2 | ≤5% | |
| BB94 | 15 μmol/L | 0.1 ± 0.0 | ≤5% | |
| Angiotensin converting enzyme inhibitors | Lisinopril Enalapril | 10 mmol/L 10 mmol/L | 1.1 ± 0.4 0.4 ± 0.2 | ≤5% ≤5% |
| Neutral endopeptidase inhibitor | Phosphoramidon | 10 mmol/L | 16 ± 3.2 | ≤5% |
| Aspartic protease inhibitor | Pepstatin A | 10 mmol/L | 0.2 ± 0.1 | ≤5% |
| Inhibitor Class . | Inhibitor . | [Inhibitor]* . | % Inhibition† . | % Kallikrein Inhibition‡ . |
|---|---|---|---|---|
| Cysteine protease inhibitors | Antipain | 100 μmol/L | 92 ± 7.1 | ≤5% |
| Cysteine | 10 mmol/L | 99 ± 3.4 | ≤5% | |
| HgCl2 | 1 mmol/L | 96 ± 3.6 | ≤5% | |
| DTT | 10 mmol/L | 99 ± 3.5 | 28.6% | |
| 2-Mercaptoethanol | 5% | 98 ± 2.3 | ≤5% | |
| Glutathione | 100 μmol/L | 62 ± 4.5 | 10.4% | |
| Calpain Inhibitor | 10 mmol/L | 46 ± 3.6 | ≤5% | |
| Z-Phe-OH | 1 mmol/L | 45 ± 2.4 | ≤5% | |
| E64 | 10 mmol/L | 2.5 ± 3.8 | ≤5% | |
| Iodoacetamide | 10 mmol/L | 2.5 ± 1.5 | ≤5% | |
| Iodoacetic Acid | 10 mmol/L | 3.1 ± 1.8 | ≤5% | |
| N-ethylmalimide | 3 mmol/L | 0.3 ± 0.1 | Not done | |
| Cystatin | 1 mmol/L | 1.0 ± 0.3 | ≤5% | |
| OH-Mercuribenoic Acid | 10 mmol/L | 1.2 ± 0.1 | ≤5% | |
| Metalloprotease inhibitors | Zincov | 100 μmol/L | 20 ± 2.5 | ≤5% |
| TIMP-1 | 20 μg/mL | 15 ± 2.9 | ≤5% | |
| TIMP-2 | 20 μg/mL | 0.4 ± 0.2 | ≤5% | |
| BB94 | 15 μmol/L | 0.1 ± 0.0 | ≤5% | |
| Angiotensin converting enzyme inhibitors | Lisinopril Enalapril | 10 mmol/L 10 mmol/L | 1.1 ± 0.4 0.4 ± 0.2 | ≤5% ≤5% |
| Neutral endopeptidase inhibitor | Phosphoramidon | 10 mmol/L | 16 ± 3.2 | ≤5% |
| Aspartic protease inhibitor | Pepstatin A | 10 mmol/L | 0.2 ± 0.1 | ≤5% |
*The values given represent the lowest concentration that gave the maximal level of inhibition of kallikrein-generating activity.
The values given represent the mean ± SD of inhibition of the prekallikrein-activating enzyme associated with HUVECs.
The values given represent the percentage of inhibition of kallikrein itself by the protease inhibitor.