TABLE 3.
Inhibitory activities of KAY-2-41, KAH-39-149, and BVDU on dThd phosphorylation and phosphorylation of these drugs by 2′-deoxynucleoside kinases from different origins
| Compound | IC50 (μM) fora: |
% of nucleoside monophosphate formb |
||||||
|---|---|---|---|---|---|---|---|---|
| HSV-1 TK | VZV TK | TK1 | TK2 | HSV-1 TK | VZV TK | TK1 | TK2 | |
| KAY-2-41 | 49 ± 1 | 272 ± 21 | ≥500 | 321 ± 16 | 0.6 ± 0.07 | 0.5 ± 0.2 | 0.9 ± 0.2 | 2.3 ± 0.4 |
| KAH-39-149 | 3.0 ± 0 | 1.4 ± 0.7 | 26 ± 11 | 6.2 ± 2.3 | 0.5 ± 0.04 | 0.7 ± 0.1 | 0.9 ± 0.3 | 4.8 ± 0.01 |
| BVDU | 2.6 ± 1.5 | 1.5 ± 0.4 | >500 | 0.4 ± 0.05 | 7.0 ± 0.04 | 5.8 ± 0.3 | 0 | 17 ± 1.3 |
| 4′-Thiothymidine | 0.09c | 6.3c | ||||||
The IC50 is the 50% inhibitory concentration of the test compounds, which was calculated as the compound concentration required to inhibit TK-catalyzed [methyl-3H]dThd (1μM) phosphorylation by 50%. The data are mean values from two independent experiments ± SD.
Values represent the percentage of the respective drug monophosphate form present in the reaction mixture after 120 min of incubation of the nucleoside with viral or cellular TK. The data are the mean values of two independent experiments ± SD.
Mean values of two experiments. The SD was never ±20% of each reported value (data from reference 26).