TABLE 2.
Potency and selectivity profile of marimastat, compound 8, and compound 11 against a panel of metalloproteases
Ki values are reported for each MP with the exception of ADAMTS-4 and -5 and BAC where IC50 values are reported.
| Metalloproteinase | Km | Calculated Ki values |
||
|---|---|---|---|---|
| Marimastat | Compound 8 | Compound 11 | ||
| μm | nm | |||
| ADAMTS-4 (IC50) | 79 | 65 | 3 | |
| ADAMTS-5 (IC50) | 106 | 93 | 17 | |
| BAC (IC50) | 5,290 | 1,700 | 624 | |
| Assayed with substrate 1a | ||||
| MMP-1 | 16 | 0.2 | >8,000 | >8,000 |
| MMP-2 | 17 | 0.2 | >8,095 | 4,995 |
| MMP-7 | 26 | 1.3 | >8,667 | 3,519 |
| MMP-8 | 20 | 0.2 | 3,800 | 321 |
| MMP-9 | 5 | 0.4 | 4144 | 1,261 |
| MMP-10 | >100 | 18 | >10,000 | NDb |
| MMP-12 | 22 | 0.2 | 553 | ND |
| MMP-13 | 4 | 0.3 | >5,000 | 2,970 |
| MMP-26 | >100 | 0.4 | 3,980 | ND |
| MT1-MMP | 8 | 1.1 | 5,300 | >6,667 |
| MT2-MMP | 17 | 1.1 | 6,387 | ND |
| MT3-MMP | 7 | 0.4 | 6,077 | ND |
| MT5-MMP | 12 | 0.8 | 5,228 | ND |
| Assayed with substrate 2c | ||||
| MMP-3 | 13 | 15 | >7,647 | 4,680 |
| Assayed with substrate 3d | ||||
| ADAM-17 | 66 | 11 | 5,572 | ND |
a Substrate 1: Mca-Arg-Pro-Leu-Gly↓Leu-Dpa-Ala-Arg-Glu-Arg-NH2.
b ND, not determined.
c Substrate 2: Mca-Arg-Pro-Lys-Pro-Val-Glu↓Nva-Trp-Arg-Lys(Dnp)-NH2.
d Substrate 3: Mca-Pro-Leu-Ala-Gln-Ala↓Val-Dpa-Arg-Ser-Ser-Ser-Arg-NH2.