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Evaluate the effectiveness of dual FLT3/MAPK14 PROTACs in inducing cell death in acute myeloid leukemia.

May 24, 2026PharmaceuticalsOpen Access

Dual FLT3/MAPK14 Proteolysis-Targeting Chimera (PROTAC) Induces Potent Acute Myeloid Leukemia Cell Death

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Randomized trial demonstrates potent cell death in FLT3-ITD+ AML cells using dual-targeting PROTACs, suggesting a new treatment approach.

Evaluate the effectiveness of dual FLT3/MAPK14 PROTACs in inducing cell death in acute myeloid leukemia.
Developed FLT3-targeting PROTACs with linker modifications to enhance degradation efficiency.
Conducted cellular assays to assess apoptosis in FLT3-ITD+ AML cells.
MA190 and MA191 achieved >95% reduction in FLT3-ITD levels at nanomolar concentrations.
Both compounds induced potent apoptosis specifically in FLT3-ITD+ AML cells with minimal effects on wild-type FLT3 cells.
MA191 also degraded MAPK14, enhancing pro-apoptotic signaling and caspase-3 activation.

Abdelsalam et al. (2026) studied this question.

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