Effects of various cytidine analogs on the uptake of uridine in S. cerevisiae producing pYPhENT1, pYPhENT2, pYPhCNT1, pYPhCNT2, or pYPhCNT3
Presented are EC50 values, which represent the effective concentrations at which the uptake of 1 μM [3H]uridine was inhibited by 50% over a 20-min time period as determined by computer-generated concentration-effect curves (see Fig. 4). The corresponding Ki values are given in parentheses, where Ki = EC50/1 + ([S]/Km) (Cheng and Prusoff 1973). In these calculations, [S] = 1.0 μM and Km (uridine/hENT1) = 44.2 μM; Km (uridine/hENT2) = 195 μM; Km (uridine/hCNT1) = 55.4 μM; and Km (uridine/hCNT2) = 29.1 μM and Km (uridine/hCNT3) = 8.7 μM.
| Compound | EC50 (Ki) | ||||
|---|---|---|---|---|---|
| hENT1 | hENT2 | hCNT1 | hCNT2 | hCNT3 | |
| μM | |||||
| Cytidine | 171 (167) | 650 (647) | 17 (16.4) | 1445 (1397) | 5 (4) |
| 2′-Deoxycytidine | 288 (282) | 1035 (1030) | 9 (8.6) | 1714 (1657) | 7 (6.3) |
| Gemcitabine | 362 (354) | 784 (780) | 13.4 (13) | 1365 (1320) | 25 (22.3) |
| AraC | 788 (771) | 760 (756) | >2000a | >10,000a | >10,000a |
| TaraC | >1000a | >3000a | 459 (451) | >3000a | >2000a |
| 3′-Deoxycytidine | >2000a | >10,000a | >2000a | >20,000a | >10,000a |
| 2′,3′-Dideoxycytidine | >10,000a | >20,000a | >5000a | >20,000a | >10,000a |
↵ a Ki values were not calculated due to high EC50 values.