MA191 is an FLT3 PROTAC degrader that effectively addresses FLT3 inhibitor resistance caused by the rebound activation of mitogen-activated kinases. It rapidly degrades FLT3-ITD via a mechanism involving VHL, Neddylation, and BIM, reducing FLT3-ITD levels prior to inducing apoptosis. Moreover, MA191 inhibits the proliferation of AML cells in zebrafish and is applicable for acute myeloid leukemia (AML) research.