Table 3.
Inhibition of murine COX-2 mutants by NSAID ester and amide derivatives
| Mutant | IC50, μM*
|
|||||
|---|---|---|---|---|---|---|
| Indomethacin | Ester 8 | Amide 19 | Bromobenzyl analog 23 | Meclofenamic acid | Amide 27 | |
| Wild-type mouse COX-2 | 0.21 | 0.050 | 0.26 | 3.8 | 0.13 | 0.40 |
| R120Q | >2.5 (0% inhibition) | 0.070 | 0.17 | |||
| R120A | >2.5 (20% inhibition) | 0.060 | >2.5 | >5.0 (0% inhibition) | 0.42 | 0.55 |
| Y355F | >5.0 (8% inhibition) | >5.0 (10% inhibition) | >5.0 (8% inhibition) | >3.0 (0% inhibition) | >3.0 (30% inhibition) | |
| E524L | 0.28 | >5.0 (22% inhibition) | >5.0 (25% inhibition) | 0.37 | 0.90 | |
| L503F | 0.53 | 0.36 | >2.5 (35% inhibition) | >5.0 (8% inhibition) | 0.13 | 0.5 |
| S530A | 0.22 | 0.080 | 0.70 | 0.13 | 0.13 | |
| V523I | 0.45 | 0.20 | 0.98 | |||
| V523IR513HV434I | 2.1 | 0.17 | 1.1 | 0.30 | 0.30 | |
*
IC50 values in μM represent time-dependent inhibition and average determinations from three experiments. The amino acid designations are based on the COX-1 amino acid sequence.