Vascular endothelial growth factor receptor 1 (VEGFR1) (VEGFR1)

Vascular endothelial growth factor receptor 1 (VEGFR1), also known as Fms-like tyrosine kinase 1 (FLT1), is a high-affinity cell-surface receptor for VEGF-A, VEGF-B, and placental growth factor (PlGF) [1]. It belongs to the receptor tyrosine kinase (RTK) family and is characterized by an extracellular ligand-binding domain, a transmembrane segment, and an intracellular tyrosine kinase domain [1, 2]. In vascular development, VEGFR1 acts as a decoy receptor by sequestering VEGF-A, thereby negatively regulating VEGFR2 signaling; however, its kinase activity is essential for recruiting macrophages and promoting cell migration in pathological contexts like cancer and inflammation [3]. Therapeutic targeting of the VEGFR1 kinase domain is primarily achieved through small-molecule multi-kinase inhibitors (TKIs) that block ATP binding [4, 5]. These drugs are widely used to treat various malignancies by inhibiting tumor angiogenesis and lymphangiogenesis [4]. Beyond oncology, dysregulation of VEGFR1, particularly its soluble form (sFlt-1), is a key factor in the pathogenesis of preeclampsia and certain ocular diseases [2, 3].

Other names

Fms-like tyrosine kinase 1FLT1FLT-1VEGFR-1Tyrosine-protein kinase FRT

Small-molecule inhibitors bind to the intracellular kinase domain of VEGFR1, typically competing with ATP for the binding site, which prevents autophosphorylation and subsequent activation of downstream signaling pathways such as MAPK/ERK and PI3K/Akt.