Cellular IC50 values of Bcr-Ab1 point mutants that were identified
Mutation . | Imatinib, μM . | Fold, IC50 wt . | PD166326, nM . | Fold IC50 wt . |
|---|---|---|---|---|
| Wild-type | 0.4 | — | 5 | — |
| M2371 | 1 | 2.5 | 13 | 2.6 |
| M244V | 2.3 | 5.8 | 33 | 6.6 |
| L248V | 1.5 | 3.8 | 23 | 4.6 |
| G250A | 0.3 | 1 | 6 | 1.2 |
| G250E | 3.9 | 7.5 | 100 | 20 |
| G250V | 0.8 | 2 | 31 | 6.2 |
| Q252H | 1.2 | 3 | 25 | 5 |
| E255D | 0.6 | 1.5 | 14 | 2.8 |
| E255R | 3.5 | 8.8 | 24 | 4.8 |
| E275K | 2.9 | 7.3 | 23 | 4.6 |
| D276G | 1.5 | 3.8 | 19 | 3.8 |
| E281K | 1.2 | 3 | 14 | 2.8 |
| K285N | 0.9 | 2.3 | 5 | 1 |
| F311V | 5.4 | 13.5 | 47 | 9.4 |
| F317C | 1.2 | 3 | 110 | 22 |
| F317L | 1.5 | 3.8 | 70 | 14 |
| F317V | 0.5 | 1.3 | 135 | 27 |
| D325N | 1.5 | 3.8 | 12 | 2.4 |
| S348L | 0.7 | 1.4 | 5 | 1 |
| M351L | 0.9 | 2.3 | 7 | 1.4 |
| E355A | 1.2 | 3 | 16 | 3.2 |
| E355G | 0.4 | 1 | 7 | 1.4 |
| F359C | 1.2 | 3 | 50 | 10 |
| F359V | 1.2 | 3 | 45 | 9 |
| A380S | 6.2 | 15.5 | 22 | 4.4 |
| L387F | 1.1 | 2.8 | 20 | 4 |
| M388L | 1.6 | 4 | 16 | 3.2 |
Mutation . | Imatinib, μM . | Fold, IC50 wt . | PD166326, nM . | Fold IC50 wt . |
|---|---|---|---|---|
| Wild-type | 0.4 | — | 5 | — |
| M2371 | 1 | 2.5 | 13 | 2.6 |
| M244V | 2.3 | 5.8 | 33 | 6.6 |
| L248V | 1.5 | 3.8 | 23 | 4.6 |
| G250A | 0.3 | 1 | 6 | 1.2 |
| G250E | 3.9 | 7.5 | 100 | 20 |
| G250V | 0.8 | 2 | 31 | 6.2 |
| Q252H | 1.2 | 3 | 25 | 5 |
| E255D | 0.6 | 1.5 | 14 | 2.8 |
| E255R | 3.5 | 8.8 | 24 | 4.8 |
| E275K | 2.9 | 7.3 | 23 | 4.6 |
| D276G | 1.5 | 3.8 | 19 | 3.8 |
| E281K | 1.2 | 3 | 14 | 2.8 |
| K285N | 0.9 | 2.3 | 5 | 1 |
| F311V | 5.4 | 13.5 | 47 | 9.4 |
| F317C | 1.2 | 3 | 110 | 22 |
| F317L | 1.5 | 3.8 | 70 | 14 |
| F317V | 0.5 | 1.3 | 135 | 27 |
| D325N | 1.5 | 3.8 | 12 | 2.4 |
| S348L | 0.7 | 1.4 | 5 | 1 |
| M351L | 0.9 | 2.3 | 7 | 1.4 |
| E355A | 1.2 | 3 | 16 | 3.2 |
| E355G | 0.4 | 1 | 7 | 1.4 |
| F359C | 1.2 | 3 | 50 | 10 |
| F359V | 1.2 | 3 | 45 | 9 |
| A380S | 6.2 | 15.5 | 22 | 4.4 |
| L387F | 1.1 | 2.8 | 20 | 4 |
| M388L | 1.6 | 4 | 16 | 3.2 |
Ba/F3 cells transfected with engineered mutant forms of Bcr-Abl were cultured for 24 and 48 hours without and in the presence of imatinib and PD166326 at concentrations as stated in Figure 3. Proliferation was measured in an MTS-based assay. There were 2 independent experiments performed. IC50 values were calculated using representative results of one experiment after 48 hours of incubation. Y253H, E255K, E255V, and T315I have been shown previously.8,18