Table 3. Enzyme Inhibitory Profile of I10H Analogues.
| Protease a/nM | Substrate a/μM | IC50 (N = 3) /nM b | ||||
|---|---|---|---|---|---|---|
| Native SFTI | I10H | Analogue 1 | Analogue 2 | Analogue 6 | ||
| Bovine Trypsin (10) | Boc-VPR-AMC (21) | 19 ±1 | 46 ±2 | n.d. | 20 ±0.2 | 23 ±1 |
| KLK14 (10) | Boc-VPR-AMC (45) | 30 ±7 | 470 ±47 | n.d. | 85 ±6 | 24 ±2 |
| KLK5 (10) | Boc-VPR-AMC (42) | 230 ±3 (Ki = 210) | 523 ±11 (Ki = 478) | n.d. | 100 ±2 (Ki = 91) | 56 ±0.5 (Ki = 51) |
| KLK8 (9) | Boc-VPR-AMC (42) | 1286 ±251 | 1683 ±51 | n.d. | 563 ±14 | 373 ±31 |
| Matriptase (10) | Boc-VPR-AMC (21) | 1254 ±57 | 2244 ±567 | n.d. | 206 ±10 | 381 ±12 |
| Human Plasma Plasmin (24) | Boc-VPR-AMC (42) | 24 ±4 | 161 ±6 | n.d. | 25 ±1 | 407 ±8 |
| KLK7 (10) | BODIPY_FL (Casein 6.5 μg/mL) | 18% inhibition at 11 μM | 0% inhibition at 11 μM | 2289 ±68 | 28% inhibition at 11 μM | 534 ±29 |
| Human Neutrophil Elastase (10) | MeOSuc-AAPV-AMC (41) | 0% inhibition at 10 μM | 0% inhibition at 10 μM | n.d. | 0% inhibition at 10 μM | 0% inhibition at 10 μM |
| Porcine Pancreatic Elastase 1 (46) | MeOSuc-AAPV-AMC (41) | 0% inhibition at 10 μM | 0% inhibition at 10 μM | n.d. | 0% inhibition at 10 μM | 0% inhibition at 10 μM |
| Human Plasma Kallikrein (14) | Boc-VPR-AMC (42) | 0% inhibition at 10 μM | 0% inhibition at 10 μM | n.d. | 0% inhibition at 10 μM | 15% inhibition at 10 μM |
a value denoted in bracket is the final assay concentration.
b Fitted IC50 curves (except KLK5) of each tested ligand are displayed in S3 Fig.
n.d.: Not Determined.