Progress in the Development of PROTAC Degraders of FLT3

Abstract Fms‐like tyrosine kinase 3 (FLT3) is a well‐characterized therapeutic target for acute myeloid leukemia (AML). Despite the approval of two generations of small molecular FLT3 kinase inhibitors for AML treatment, the acquired drug resistance inevitably emerges. Moreover, the complete and sustained suppression of FLT3 signaling was demonstrated to be required for an effective clinical response, but it is challenging to achieve this goal with kinase inhibitors that work in an occupancy‐driven manner. Targeting protein degradation by proteolysis targeting chimera (PROTAC) is a catalytic and event‐driven process, and several PROTAC degraders for FLT3 have been developed. This review focuses on the latest research progress on FLT3 degraders, providing a systematic perspective and in‐depth insights for targeted therapy of FLT3‐mutated AML.