Vascular endothelial growth factor receptor 1-3 (VEGFR1-3) (VEGFR1-3)

Vascular endothelial growth factor receptors (VEGFR1, VEGFR2, and VEGFR3) are a family of receptor tyrosine kinases that serve as master regulators of angiogenesis, lymphangiogenesis, and vascular permeability [1, 3]. These receptors are characterized by an extracellular ligand-binding domain and an intracellular tyrosine kinase domain that mediates signal transduction [1]. Upon binding of VEGF ligands, the receptors undergo dimerization and autophosphorylation of their kinase domains, triggering downstream pathways such as MAPK/ERK and PI3K/Akt that promote endothelial cell survival and migration [2, 3]. In many malignancies, the overactivation of these receptors facilitates tumor growth and metastasis by stimulating the formation of new blood and lymphatic vessels [3, 4]. Consequently, the kinase domains of VEGFR1-3 are primary therapeutic targets for small-molecule tyrosine kinase inhibitors (TKIs) used in the treatment of various solid tumors, including renal cell carcinoma and hepatocellular carcinoma, as well as neovascular ocular diseases [2, 5, 6].

Other names

VEGF receptor tyrosine kinase domainsFlt-1/KDR/Flt-4VEGFR familyVascular endothelial growth factor receptor kinase domains

Small-molecule inhibitors competitively bind to the adenosine triphosphate (ATP) binding pocket within the intracellular tyrosine kinase domains of VEGFR1, VEGFR2, and VEGFR3, thereby preventing receptor autophosphorylation and the subsequent activation of downstream signaling cascades [2, 6].