TABLE 4.
Susceptibilities of wild-type and mutant IN to IN inhibitors
| IN enzyme | IC50 (μM) (fold resistance)a
|
||
|---|---|---|---|
| L-708,906 | S-1360 | V-165 | |
| Wild type | 0.069 ± 0.015 | 1.05 ± 0.19 | 4.78 ± 0.16 |
| Mutant | |||
| T66I | 0.061 ± 0.008 (0.9) | 0.68 ± 0.33 (0.6) | 18.71 ± 2.30 (3.9) |
| L74M | 0.121 ± 0.051 (1.8) | 0.66 ± 0.22 (0.6) | 3.95 ± 0.82 (0.8) |
| S230R | 0.084 ± 0.040 (1.2) | 1.36 ± 0.09 (1.3) | 11.22 ± 3.85 (2.3) |
| T66I L74M | 0.104 ± 0.012 (1.5) | 1.08 ± 0.38 (1.0) | 4.57 ± 0.05 (1.0) |
| T66I L74M S230R | 0.154 ± 0.010 (2.2) | 3.78 ± 0.34 (3.6) | 6.48 ± 1.34 (1.4) |
a
IC50 or concentration of the compound required to inhibit the overall integrase activity of each enzyme by 50%. Enzymes were used at concentrations resulting in comparable enzymatic activities. Fold increase in the IC50 of the compound against the mutant enzyme compared to the IC50 of the compound against wild-type IN is shown in parentheses. Boldface values indicate reduced susceptibility compared to that of the wild-type IN.