Acute Myeloid Leukemia (AML) is a complex hematologic malignancy characterized by the rapid proliferation of abnormal myeloid precursor cells. The FMS-like tyrosine kinase 3 (FLT3), a receptor tyrosine kinase, plays a pivotal role in regulating cell survival, proliferation, and differentiation within the hematopoietic system. Mutations in FLT3, particularly internal tandem duplications (ITDs) and point mutations within the tyrosine kinase domain (TKD), are prevalent in AML and are associated with poor prognosis and increased risk of relapse. The development of targeted therapies has revolutionized the landscape of cancer treatment by focusing on the inhibition of kinase signalling. Small-molecule inhibitors designed to selectively target receptor tyrosine kinases, such as PLX3397, have shown promising results in preclinical studies and early phase clinical trials. PLX3397 exerts its inhibitory effects by targeting CSF1R and KIT, leading to the disruption of receptor tyrosine kinase signalling cascades, suppression of leukemic cell growth, and induction of apoptosis. This study emphasizes the significance of FLT3 as a receptor tyrosine kinase as a therapeutic target for PLX3397. After evaluating the usefulness of PLX3397 as an enzyme inhibitor using ADMET prediction, PLX3397 was prepared for molecular docking in the FLT3 crystal structure (PDB: 4XUF). A molecular dynamics simulation was performed on PLX3397 to evaluate its binding affinity and protein stability in a simulated physiological environment. In conclusion, targeting FLT3 as a receptor tyrosine kinase with PLX3397 represents a promising therapeutic strategy for improving outcomes in patients with FLT3-mutated AML. Further clinical investigations are warranted to validate the efficacy and safety of PLX3397 and to optimize treatment strategies for AML patients based on the FLT3 mutational status.

AML, FLT3, PLX3397, targeted therapy, receptor tyrosine kinase.