Fms-related tyrosine kinase 1 and Fms-related tyrosine kinase 3 (FLT1/3)

Fms-related tyrosine kinase 1 (FLT1, also known as VEGFR1) and Fms-related tyrosine kinase 3 (FLT3) are distinct members of the receptor tyrosine kinase (RTK) family that are frequently grouped in pharmacological profiling due to their structural similarity and common inhibition by multi-kinase inhibitors. FLT1 is a key regulator of angiogenesis and vascular homeostasis, binding to VEGF-A, VEGF-B, and placental growth factor (PlGF) to modulate endothelial cell signaling and often acting as a decoy receptor to regulate ligand availability. FLT3 is primarily expressed in hematopoietic progenitor cells and is essential for the development of the immune and blood systems. Mutations in FLT3, particularly internal tandem duplications (ITD), are major drivers of acute myeloid leukemia (AML) and represent a significant therapeutic target. While FLT1 is targeted primarily to inhibit tumor angiogenesis and manage conditions like preeclampsia, FLT3 is a primary target in hematologic malignancies. Therapeutic agents such as midostaurin, gilteritinib, and sunitinib target these kinases by binding to the ATP-binding pocket of the intracellular kinase domain, though their multi-target nature often leads to a complex safety profile including hypertension and myelosuppression.

Other names

VEGFR1Vascular endothelial growth factor receptor 1Fms-like tyrosine kinase 1Fms-like tyrosine kinase 3CD135STK1FLK2FRT

Inhibition of the intracellular tyrosine kinase domain, preventing autophosphorylation and downstream signaling pathways such as PI3K/AKT, MAPK/ERK, and STAT5.