Vascular endothelial growth factor receptor 2 and Vascular endothelial growth factor receptor 1 (VEGFR2 / VEGFR1)

Vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2) are critical receptor tyrosine kinases that mediate the effects of vascular endothelial growth factors (VEGFs) on the cardiovascular and lymphatic systems. VEGFR2 is the primary transducer of VEGF-A signals, driving endothelial cell proliferation, migration, and survival, which are essential for angiogenesis and vascular permeability (UniProt P35968). While VEGFR1 has a higher affinity for VEGF-A, it possesses weaker kinase activity and often functions as a decoy receptor to modulate VEGF availability, though it also plays roles in macrophage recruitment and pathological angiogenesis (UniProt P17948). In many cancers, these receptors are overexpressed or overstimulated, promoting the formation of new blood vessels that supply nutrients to tumors and facilitate metastasis (PubMed: 15322550). Consequently, VEGFR1 and VEGFR2 are major therapeutic targets in oncology and ophthalmology. Drugs targeting these receptors include small-molecule tyrosine kinase inhibitors (TKIs) like sunitinib and sorafenib, as well as monoclonal antibodies like ramucirumab, which aim to starve tumors of their blood supply or reduce pathological leakage in retinal diseases (NIH: StatPearls).

Other names

VEGFR-2VEGFR-1Kinase insert domain receptor (KDR)Fetal liver kinase 1 (FLK1)Fms-like tyrosine kinase 1 (FLT1)CD309CD338

Competitive inhibition of the ATP-binding site within the intracellular tyrosine kinase domain, or blocking the extracellular ligand-binding domain to prevent receptor dimerization and downstream signaling cascades such as MAPK/ERK and PI3K/Akt.