In vitro dose-response curve parameters, calculated IPP, and rate of CCyR (%)5,6 for 3 ABL TKIs in various BCR-ABL mutants
| . | Imatinib . | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | WT . | M244V . | G250E . | Q252H . | Y253F . | Y253H . | E255K . | E255V . | F311L . | F317L . | M351T . | F359V . | V379I . | L387M . | H396P . | H396R . |
| R2 | 0.96 | 0.88 | 0.98 | 0.98 | 0.99 | 0.99 | 0.98 | 0.93 | 0.93 | 0.99 | 0.99 | 0.94 | 0.94 | 0.97 | 0.94 | 0.92 |
| Slope | 1.87 | 5 | 1.3 | 2 | 3.7 | 1.4 | 1.46 | 0.43 | 2.6 | 3.28 | 3.3 | 2.5 | 2.6 | 2.2 | 2.66 | 3.2 |
| IC50 | 274.5 | 1919.8 | 1184.3 | 854.1 | 3321.3 | 20508.0 | 5227.3 | 88907.2 | 419.2 | 982 | 942.5 | 897.8 | 1139.6 | 914.3 | 747.4 | 1096.6 |
| IPP | 4.82 | 3.19 | 1.66 | 2.93 | 0.85 | 0.084 | 0.46 | 0.22 | 5.59 | 4.28 | 4.43 | 3.50 | 3.04 | 3.06 | 4.20 | 3.83 |
| . | Imatinib . | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | WT . | M244V . | G250E . | Q252H . | Y253F . | Y253H . | E255K . | E255V . | F311L . | F317L . | M351T . | F359V . | V379I . | L387M . | H396P . | H396R . |
| R2 | 0.96 | 0.88 | 0.98 | 0.98 | 0.99 | 0.99 | 0.98 | 0.93 | 0.93 | 0.99 | 0.99 | 0.94 | 0.94 | 0.97 | 0.94 | 0.92 |
| Slope | 1.87 | 5 | 1.3 | 2 | 3.7 | 1.4 | 1.46 | 0.43 | 2.6 | 3.28 | 3.3 | 2.5 | 2.6 | 2.2 | 2.66 | 3.2 |
| IC50 | 274.5 | 1919.8 | 1184.3 | 854.1 | 3321.3 | 20508.0 | 5227.3 | 88907.2 | 419.2 | 982 | 942.5 | 897.8 | 1139.6 | 914.3 | 747.4 | 1096.6 |
| IPP | 4.82 | 3.19 | 1.66 | 2.93 | 0.85 | 0.084 | 0.46 | 0.22 | 5.59 | 4.28 | 4.43 | 3.50 | 3.04 | 3.06 | 4.20 | 3.83 |
| . | Nilotinib . | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | WT . | M244V . | G250E . | Q252H . | Y253F . | Y253H . | E255K . | E255V . | F311L . | F317L . | M351T . | F359V . | V379I . | L387M . | H396P . | H396R . |
| R2 | 0.99 | 0.99 | 0.99 | 0.97 | 0.97 | 0.94 | 0.98 | 0.94 | 0.98 | 0.99 | 0.99 | 0.99 | 0.94 | 0.96 | 0.99 | 0.99 |
| Slope | 2.1 | 5.64 | 1.66 | 0.94 | 4.06 | 1.13 | 3.1 | 0.98 | 3.08 | 2.88 | 2.84 | 2.72 | 2.56 | 1.58 | 2.5 | 2.95 |
| IC50 | 14.3 | 47.7 | 59.8 | 41.4 | 107.7 | 616.9 | 174.4 | 600.6 | 24.9 | 47.2 | 16.9 | 148.4 | 44.2 | 53.9 | 41.3 | 37.6 |
| IPP | 12.0 | 25.3 | 7.1 | 4.4 | 14.9 | 2.3 | 9.9 | 2.1 | 15.8 | 13.0 | 15.7 | 9.1 | 11.7 | 6.9 | 11.6 | 14.0 |
| CCyR% | 35 | 60 | 25 | 0 | 0 | 27 | 13 | 20 | ||||||||
| . | Nilotinib . | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | WT . | M244V . | G250E . | Q252H . | Y253F . | Y253H . | E255K . | E255V . | F311L . | F317L . | M351T . | F359V . | V379I . | L387M . | H396P . | H396R . |
| R2 | 0.99 | 0.99 | 0.99 | 0.97 | 0.97 | 0.94 | 0.98 | 0.94 | 0.98 | 0.99 | 0.99 | 0.99 | 0.94 | 0.96 | 0.99 | 0.99 |
| Slope | 2.1 | 5.64 | 1.66 | 0.94 | 4.06 | 1.13 | 3.1 | 0.98 | 3.08 | 2.88 | 2.84 | 2.72 | 2.56 | 1.58 | 2.5 | 2.95 |
| IC50 | 14.3 | 47.7 | 59.8 | 41.4 | 107.7 | 616.9 | 174.4 | 600.6 | 24.9 | 47.2 | 16.9 | 148.4 | 44.2 | 53.9 | 41.3 | 37.6 |
| IPP | 12.0 | 25.3 | 7.1 | 4.4 | 14.9 | 2.3 | 9.9 | 2.1 | 15.8 | 13.0 | 15.7 | 9.1 | 11.7 | 6.9 | 11.6 | 14.0 |
| CCyR% | 35 | 60 | 25 | 0 | 0 | 27 | 13 | 20 | ||||||||
| . | Dasatinib . | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | WT . | M244V . | G250E . | Q252 H . | Y253F . | Y253H . | E255K . | E255V . | F311L . | F317L . | M351T . | F359V . | V379I . | L387M . | H396P . | H396R . |
| R2 | 0.99 | 0.99 | 0.98 | 0.98 | 0.97 | 0.97 | 0.95 | 0.94 | 0.97 | 0.93 | 0.94 | 0.99 | 0.95 | 0.97 | 0.95 | 0.98 |
| Slope | 1.82 | 3.5 | 1.54 | 1.46 | 3.35 | 2.55 | 1.41 | 0.99 | 3.1 | 1.8 | 2.74 | 2.39 | 1.87 | 2.27 | 3.87 | 1.96 |
| IC50 | 1.2 | 1.3 | 1.5 | 1.2 | 1.2 | 1.1 | 5.6 | 11.3 | 1.1 | 6.2 | 1.0 | 1.8 | 1.5 | 1.5 | 1.8 | 1.1 |
| IPP | 7.8 | 14.8 | 6.4 | 6.4 | 14.5 | 11.3 | 3.9 | 2.2 | 13.7 | 4.8 | 12.3 | 9.4 | 7.6 | 9.2 | 15.1 | 8.7 |
| CCyR% | 56 | 43 | 33 | 17 | 61 | 38 | 36 | 7 | 46 | 52 | 8O | 39 | ||||
| . | Dasatinib . | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | WT . | M244V . | G250E . | Q252 H . | Y253F . | Y253H . | E255K . | E255V . | F311L . | F317L . | M351T . | F359V . | V379I . | L387M . | H396P . | H396R . |
| R2 | 0.99 | 0.99 | 0.98 | 0.98 | 0.97 | 0.97 | 0.95 | 0.94 | 0.97 | 0.93 | 0.94 | 0.99 | 0.95 | 0.97 | 0.95 | 0.98 |
| Slope | 1.82 | 3.5 | 1.54 | 1.46 | 3.35 | 2.55 | 1.41 | 0.99 | 3.1 | 1.8 | 2.74 | 2.39 | 1.87 | 2.27 | 3.87 | 1.96 |
| IC50 | 1.2 | 1.3 | 1.5 | 1.2 | 1.2 | 1.1 | 5.6 | 11.3 | 1.1 | 6.2 | 1.0 | 1.8 | 1.5 | 1.5 | 1.8 | 1.1 |
| IPP | 7.8 | 14.8 | 6.4 | 6.4 | 14.5 | 11.3 | 3.9 | 2.2 | 13.7 | 4.8 | 12.3 | 9.4 | 7.6 | 9.2 | 15.1 | 8.7 |
| CCyR% | 56 | 43 | 33 | 17 | 61 | 38 | 36 | 7 | 46 | 52 | 8O | 39 | ||||