Table 1.
Sensitivity of WT and DKO to DHFR–TS and PTR1 inhibitors.
| WT | DKO | Ratio DKO/WT | ||||||
|---|---|---|---|---|---|---|---|---|
| Inhibitor | EC50 HMI9 (μM) | EC50 FDM (μM) | Ratio EC50 | EC50 HMI9 (μM) | EC50 FDM (μM) | Ratio EC50 | HMI9 | FDM |
| Methotrexate | 2.5 ± 0.2 (3)a | 0.037 ± 0.007 (2) | 68 | 17.9 ± 6.5 (2) | 22.2 ± 5.2 (2) | 0.8 | 7.2 | 484 |
| Aminopterin | 15.1 ± 2.3 (2) | 0.049 ± 0.009 (3) | 308 | 78.5 ± 5.9 (2) | 75.1 ± 6.2 (2) | 1.0 | 5.2 | 1 533 |
| Raltitrexed | 22.4 ± 2.1 (3) | 0.072 ± 0.009 (3) | 311 | > 800 (2) | > 800 (2) | − | > 36 | > 11 111 |
| Pemetrexed | 1.8 ± 0.1 (2) | 1.9 ± 0.3 (2) | 0.9 | > 800 (2) | > 800 (2) | − | > 444 | > 421 |
| Pyrimethamine | 17.2 ± 2.7 (3) | 9.6 ± 1.3 (2) | 1.8 | 35.6 ± 4.5 (2) | 27.6 ± 2.6 (2) | 1.3 | 2.1 | 2.9 |
| Trimetrexate | 1.2 ± 0.1 (3) | 3.2 ± 0.3 (3) | 0.4 | 4.1 ± 0.6 (3) | 5.6 ± 0.8 (2) | 0.7 | 1.9 | 1.8 |
| 5-Fluoro-orotic acid | 2.8 ± 0.3 (3) | 1.4 ± 0.3 (3) | 1.6 | 4.2 ± 0.7 (2) | 2.5 ± 0.5 (3) | 1.7 | 1.9 | 1.7 |
| O/129b | 16.5 ± 1.7 (3) | 7.4 ± 1.2 (2) | 2.2 | 17.9 ± 2.1 (3) | 9.7 ± 1.1 (3) | 1.8 | 0.9 | 1.3 |
| Triamterene | 48.3 ± 5.1 (2) | 45.2 ± 3.6 (2) | 1.1 | 15.9 ± 1.1 (2) | 58.9 ± 7.8 (2) | 0.3 | 0.3 | 1.3 |
a
n = number of independent experiments, where EC50 values are weighted means and standard errors of each independent determination.
b
2,4-Diamino-6,7-diisopropylpteridine.