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Molecular Mechanisms of Quizartinib Resistance in FLT3 Mutants

Quizartinib, a type II FLT3 inhibitor approved for FLT3-ITD-positive acute myeloid leukemia (AML), is frequently limited by acquired resistance, which arises in up to 40% of patients with disease progression and is driven largely by the D835Y and F691L kinase-domain mutations. To define the underlying mechanisms, we performed triplicate 200-ns all-atom molecular dynamics simulations of wild-type…

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