Table 1.
Inhibition of ITD-mutant (FLT3/ITD) and wild-type (WT) FLT3 autophosphorylation
| Drug | WT FLT3 IC50, medium, nM | FLT3/ITD IC50, medium, nM | FLT3/ITD IC50, plasma, nM | In vivo t1/2, h |
|---|---|---|---|---|
| Lestaurtinib | 10 | 2 | 700 | 825 |
| Midostaurin | 30 | 3 | 1700 | 24+26 |
| Sorafenib | 28 | 3 | 484 | 24+27 |
| Sunitinib | 2 | 1 | ND | 24+28 |
| KW-2449 | 36 | 10 | 144 | 411 |
| AC220 | 5 | 1 | 18 | 24+5 |
SEMK2 cells (wild-type FLT3) and Molm-14 cells (FLT3/ITD) were incubated with increasing concentrations of inhibitor. R values for all experiments were greater than 0.98. Sunitinib was not analyzed in plasma, as there are no active FLT3 AML trials with this agent. The plasma half-lives (In vivo t1/2) were obtained from early-phase clinical trial data (see references). ND indicates not determined.