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Figure 3 | Molecular Cancer

Figure 3

From: Quizartinib (AC220) is a potent second generation class III tyrosine kinase inhibitor that displays a distinct inhibition profile against mutant-FLT3, -PDGFRA and -KIT isoforms

Figure 3

Cellular effects of quizartinib are tyrosine kinase-mediated (A) Quizartinib displays distinct antiproliferative effects of genetically altered Ba/F3 cells in dependence of the tyrosine kinase isoform transfected. The sensitivity of inhibition of proliferation is thereby similar to the sensitivity achieved in natural leukemia cell lines harboring a similar mutation. Estimated IC50s are provided in Table 3 along with IC50s for the proapoptotic effects in the same cellular context. (B) The observed cellular effects are directly linked to the potency of inhibition of phosphorylation of mutant-KIT and FLT3 isoforms. Whole cell lysates of Ba/F3 cells transfected with different human mutant-KIT or -FLT3 isoforms were immunoblotted using a pan-phosphotyrosine antibody or a total-KIT or -FLT3 antibody. Pretreatment of cells with quizartinib revealed isoform-specific inhibition of phosphorylation. Notably, inhibition of phosphorylation of the D816V mutation was significantly reduced compared to the D816Y and D816F isoforms.

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