Growth-inhibitory effects of antifolates against AA8 and PyrR100 cells grown under different folic acid concentrations
| Antifolate | Target | Polyglutamylation | IC50 | |||
|---|---|---|---|---|---|---|
| AA8 (2.3 μM FA) | AA8 (100 nM FA) | PyrR100 (2.3 μM FA) | PyrR100 (5 nM FA) | |||
| nM | ||||||
| MTX | DHFR | + | 23 ± 1 | 3.4 ± 0.7 | 79 ± 24 | 4.9 ± 1.6 |
| EDX | DHFR | + | 1.7 ± 0.7 | 0.7 ± 0.2 | 12 ± 3 | 1.3 ± 0.8 |
| PT523 | DHFR | − | 1.8 ± 0.2 | 0.5 ± 0.2 | 20 ± 2 | 1.0 ± 0.5 |
| TMQ | DHFR | − | 10 ± 4 | 0.4 ± 0.3 | 401 ± 39 | 2.9 ± 1.5 |
| Pyr | DHFR | − | 214 ± 43 | 10 ± 6 | 150,000 | 5875 ± 1305 |
| AG377 | DHFR/TS | − | 27 ± 14 | 2.5 ± 1.5 | 820 ± 100 | 16 ± 6 |
| ZD1694 | TS | + | 17 ± 3 | 3.2 ± 0.8 | 21 ± 8 | 1.5 ± 1.0 |
| GW1843 | TS | + | 253 ± 11 | 33 ± 14 | 141 ± 51 | 2.5 ± 2.2 |
| LY231514/MTA | TS | + | 43 ± 9 | 6.9 ± 0.9 | 109 ± 40 | 3.8 ± 2.5 |
| ZD9331 | TS | − | 1665 ± 390 | 58 ± 35 | 900 ± 185 | 10 ± 8 |
| AG337 | TS | − | 20,220 ± 6750 | 1030 ± 560 | 62,280 ± 14,820 | 2385 ± 1315 |
| DDATHF | GARFT | + | 62 ± 36 | 6.2 ± 1.1 | 1600 ± 1065 | 3.0 ± 1.9 |
| AG2032 | GARFT | + | 81 ± 16 | 5.3 ± 2.2 | 96 ± 33 | 5.5 ± 2.0 |
| AG2034 | GARFT | + | 28 ± 11 | 3.2 ± 0.8 | 402 ± 222 | 2.6 ± 1.2 |
The 50% growth-inhibitory concentration (IC50 in nM) was determined after 72-h drug exposure. Results are the mean ± S.D. of three to six separate experiments.