Table 2.
Inhibitory activity of crizotinib and TAE684 on Ba/F3 cells expressing EML4-ALK mutants
| Crizotinib | TAE684 | ||||
|---|---|---|---|---|---|
| Viability (IC50s, nm) | p-ALK (IC50, nm) | Viability (IC50, nm) | p-ALK (IC50, nm) | ||
| Ba/F3 line | ENU clonea | Reintroduced | ENU clone | ENU clone | ENU clone |
| Parentalb | 1176 ± 282 | N/A | N/A | 1283 ± 348 | N/A |
| Native EML4-ALK | 132 ± 45 | N/A | 102 ± 70 | 8 ± 1 | 5 ± 3.5 |
| T1151K | 231 ± 106 | 152 ± 48 | ND | ND | ND |
| L1152V | 237 ± 25 | 162 ± 89 | ND | ND | ND |
| C1156Y | 489 ± 48 | ND | 408 ± 67 | 37 ± 5 | 11 ± 6 |
| I1171T | 393 ± 134 | 413 ± 62 | ND | ND | ND |
| F1174C | 479 ± 40 | 319 ± 90 | 165 ± 112 | 40 ± 2 | 6.7 ± 2.5 |
| L1196M | 981 ± 113 | 1215 ± 708 | 1162 ± 209 | 20 ± 3 | 3.3 ± 0.5 |
| S1206R | 681 ± 176 | 728 ± 362 | 356 ± 173 | 80 ± 9 | 16 ± 11 |
| E1210K | 318 ± 143 | 297 ± 92 | ND | ND | ND |
| F1245C | 425 ± 100 | 269 ± 194 | ND | ND | ND |
| G1269S | 953 ± 213 | 1196 ± 649 | 1366 ± 52 | 33 ± 9 | 35 ± 1 |
a
ENU clone: Ba/F3 cells obtained from the crizotinib mutagenesis screen.
b
Grown in the presence of 10 ng/mL IL-3.
ND, not determined; N/A, not applicable; ALK, anaplastic lymphoma kinase.