Figure 1.

SAR302503 can efficiently inhibit the proliferation of native and AC220-resistant variants of FLT3-ITD. (a) Dose–response sigmoidal curve showing the cellular proliferation of BAF3 cells expressing FLT3 and its kinase domain AC220 resistant variants at different concentrations of SAR302503. IC₅₀ values for each cell lines are indicated in parenthesis. (b) Bar graph showing relative fold difference in the IC₅₀ values of FLT3 mutants normalized to native FLT3-ITD. (c) Immunoblot analysis showing the kinase activity of FLT3 and its kinase domain drug resistant variants against SAR302503 at different concentrations. Blots were probed using anti-phospho-FLT3, anti-phospho-STAT5, anti-FLT3 and anti-STAT5 antibody on the crude lysates from BAF3 cells expressing FLT3 and its drug resistant variants. Please note the reduced autophosphorylation in variants ITD-D835F/Y, ITD-F691L and ITD-D839G, whereas ITD-D842H showing increased autophosphorylation in untreated samples as compared with native FLT3-ITD.