TABLE 2.
Activities of compounds against cruzipain-ΔC and human cathepsin enzymes
| Compound | Mean ± SDa IC50 (n) |
Reference | ||||||
|---|---|---|---|---|---|---|---|---|
| Cruzipain-ΔC | CatB | CatF | CatK | CatL | CatS | CatV | ||
| Cz003 (weak, neutral) | 3,700 (2) | —b | — | 1 ± 0.3 (3) | 5,990 ± 1,380 (3) | — | — | |
| Cz001 (moderate, neutral) | 170 (2) | — | — | <0.3 (2) | 2,253 (2) | — | — | |
| Cz002 (potent, neutral) | 1.2 (2) | 692 ± 177 (3) | 8 ± 2 (3) | 0.7 ± 0.7 (2) | 104 ± 52 (4) | 40 ± 12 (4) | — | |
| Cz005 (potent, basic) | 2.4 (2) | 12 ± 4 (4) | — | <0.2 (7) | 62 ± 25 (5) | 16 ± 2 (4) | — | |
| K777 (irreversible) | 3.5 (2) | 9 (2) | 3 (2) | 1.8 (2) | <0.2 (3) | <0.2 (2) | — | |
| Cz007 (potent, neutral) | 1.1 (2) | 9 ± 2 (9) | 4 ± 1 (8) | <0.5 (1) | 49 ± 19 (9) | 1.6 ± 0.2 (8) | 2 (1) | 29 |
| Cz008c (potent, basic) | 1.8 (2) | 584 ± 304 (4) | 53 ± 21 (3) | <0.005d (1) | 109 ± 11 (4) | 414 ± 141 (4) | — | 30 |
| Odanacatib (cathepsin K) | — | 1,034 | — | 0.2 | 2,995 | 60 | — | 27 |
a
Each entry is the mean concentration ± the standard deviation (with n in parentheses), unless otherwise indicated. Values may be slightly different than those reported by Beaulieu et al. (29) and Black et al. (30) due to additional testing (higher n values).
b
—, not tested.
c
Cz008 is the single diastereomer of Cz005 with the trifluoromethyl side chain stereochemistry resolved.
d
For a description of the low protein assay, see Black et al. (30).