Potency of FLT3 inhibitors in biochemical and cellular assays
| Compound . | Biochemical assay . | Cellular assays . | |||
|---|---|---|---|---|---|
| FLT3 binding affinity, Kd, nM . | FLT3 autophosphorylation . | Cell proliferation . | |||
| ITD, IC50, nM . | Wild type, IC50, nM . | MV4-11, IC50, nM . | A375, IC50, nM . | ||
| AC220 | 1.6 ± 0.7 | 1.1 ± 0.1 | 4.2 ± 0.3 | 0.56 ± 0.3 | > 10 000 |
| CEP-701 | 8.5 ± 2 | 1.5 ± 0.3 | 2.6 ± 2 | 2.1 ± 0.2 | 32 ± 9 |
| MLN-518 | 3.0 ± 0.3 | 33 ± 20 | 170 ± 50 | 60 ± 8 | > 10 000 |
| PKC-412 | 11 ± 8 | 13 ± 2 | 15 ± 9 | 12 ± 1 | 180 ± 50 |
| CGP-52421 | 68 ± 20 | 160 ± 40 | 350 ± 200 | 64 ± 8 | 530 ± 100 |
| Sorafenib | 13 ± 6 | 2.0 ± 0.3 | 3.2 ± 1 | 0.87 ± 0.6 | 2200 ± 100 |
| Sunitinib | 0.47 ± 0.2 | 34 ± 20 | 9.9 ± 6 | 4.3 ± 0.4 | 5400 ± 1000 |
| Compound . | Biochemical assay . | Cellular assays . | |||
|---|---|---|---|---|---|
| FLT3 binding affinity, Kd, nM . | FLT3 autophosphorylation . | Cell proliferation . | |||
| ITD, IC50, nM . | Wild type, IC50, nM . | MV4-11, IC50, nM . | A375, IC50, nM . | ||
| AC220 | 1.6 ± 0.7 | 1.1 ± 0.1 | 4.2 ± 0.3 | 0.56 ± 0.3 | > 10 000 |
| CEP-701 | 8.5 ± 2 | 1.5 ± 0.3 | 2.6 ± 2 | 2.1 ± 0.2 | 32 ± 9 |
| MLN-518 | 3.0 ± 0.3 | 33 ± 20 | 170 ± 50 | 60 ± 8 | > 10 000 |
| PKC-412 | 11 ± 8 | 13 ± 2 | 15 ± 9 | 12 ± 1 | 180 ± 50 |
| CGP-52421 | 68 ± 20 | 160 ± 40 | 350 ± 200 | 64 ± 8 | 530 ± 100 |
| Sorafenib | 13 ± 6 | 2.0 ± 0.3 | 3.2 ± 1 | 0.87 ± 0.6 | 2200 ± 100 |
| Sunitinib | 0.47 ± 0.2 | 34 ± 20 | 9.9 ± 6 | 4.3 ± 0.4 | 5400 ± 1000 |
Values shown are averages from at least 3 independent experiments (± SD).