IC50 values for inhibition of cell proliferation of marketed TKIs and novel small molecule BCR-ABL1 inhibitors
| . | Unmutated . | T315I . | Y253F . | Y253H . | E255K . | E255V . | M351T . | K562 cells . |
|---|---|---|---|---|---|---|---|---|
| Imatinib | 260 | >6,400 | 3,475 | >6,400 | 5,200 | >6,400 | 880 | 250-400 |
| Nilotinib | 13 | >2,000 | 125 | 450 | 200 | 430 | 15 | 30 |
| Dasatinib | 0.8 | >200 | 1.4 | 1.3 | 5.6 | 11 | 1.1 | 1 |
| DCC-2036 | 5.8 | 7.9 | 25 | — | 83 | — | 11 | 5.5 |
| MK-0457 | 100-200 | 100-200 | 100-200 | — | — | — | — | <300 |
| AP24534 | 2 | 14 | — | — | — | — | — | 60* |
| SGX393 | 12 | 7.3 | 334 | <300 | 77 | >500 | <25 | <25 |
| . | Unmutated . | T315I . | Y253F . | Y253H . | E255K . | E255V . | M351T . | K562 cells . |
|---|---|---|---|---|---|---|---|---|
| Imatinib | 260 | >6,400 | 3,475 | >6,400 | 5,200 | >6,400 | 880 | 250-400 |
| Nilotinib | 13 | >2,000 | 125 | 450 | 200 | 430 | 15 | 30 |
| Dasatinib | 0.8 | >200 | 1.4 | 1.3 | 5.6 | 11 | 1.1 | 1 |
| DCC-2036 | 5.8 | 7.9 | 25 | — | 83 | — | 11 | 5.5 |
| MK-0457 | 100-200 | 100-200 | 100-200 | — | — | — | — | <300 |
| AP24534 | 2 | 14 | — | — | — | — | — | 60* |
| SGX393 | 12 | 7.3 | 334 | <300 | 77 | >500 | <25 | <25 |
NOTE: The activity of all compounds on cell proliferation of the BCR-ABL1–positive K562 is shown for comparison. IC50, concentration of an inhibitor required for 50% inhibition of cell proliferation. All BCR-ABL1 constructs were engineered into Ba/F3 cells. All values are expressed in nmol/L.
IC90 value in K562 cells.