Peptidase potency and selectivity of neutral endopeptide (NEP) inhibitors used in this study
| Compound | Indication | Clinical Phase | NEPa | ACEa | ECE-1a | ECE-2a | IDEa | APNa | PSAa |
|---|---|---|---|---|---|---|---|---|---|
| Racecadotrilb | Diarrhea | Launched | 0.02 | 10.2 | >100 | >100 | >100 | >100 | >100 |
| Candoxatrilb | Cardiovascular | Phase 3 (halted) | 0.06 | >100 | 3.9 | 10 | >100 | 29 | >100 |
| Sacubitrilb | Cardiovascular | Launched (LCZ696) | 0.02 | >100 | 38 | 47 | >100 | 14 | >100 |
| UK-505,749 | Genitourinary | Phase 1 (halted) | 0.004 | >100 | 3.3 | 15 | >100 | >100 | >100 |
| Omapatrilat | Cardiovascular | Phase 3 (halted) | 0.04 | 0.19 | 21 | 86 | >100 | 28 | >100 |
| Gemopatrilat | Cardiovascular | Phase 1 (halted) | 0.06 | 0.23 | 12 | 77 | >100 | 18 | 18 |
| Ilepatrilc | Cardiovascular | Phase 2 (halted) | NA | NA | NA | NA | NA | NA | NA |
| MDL 100240c | Cardiovascular | Phase 2 (halted) | NA | NA | NA | NA | NA | NA | NA |
ACE, angiotensin-converting enzyme; APN, aminopeptidase N; ECE, endothelin-converting enzyme; IDE, insulin-degrading enzyme; PSA, puromycin-sensitive aminopeptidase.
↵a Mean IC50 value (μM).
↵b Peptidase activity is for the active form of this prodrug.
↵c The active form of this prodrug was not available (NA) for testing.