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

Vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2) are critical cell surface receptor tyrosine kinases that regulate the formation and maintenance of the vascular system (UniProt P17948, P35968). VEGFR2 is the primary transducer of VEGF-A signals, driving endothelial cell proliferation, migration, and survival, which are essential for angiogenesis and vascular permeability (PubMed: 10613919). While VEGFR1 has a higher affinity for VEGF-A, it often functions as a decoy receptor to sequester ligand, though it also mediates inflammatory cell recruitment and pathological vessel growth (PubMed: 11544199). In many cancers, these receptors are overexpressed or overstimulated, promoting the "angiogenic switch" that allows tumors to grow beyond a few millimeters and metastasize (StatPearls: Angiogenesis Inhibitors). Consequently, VEGFR1 and VEGFR2 are major therapeutic targets in oncology and ophthalmology. Small molecule inhibitors typically target the intracellular kinase domains of both receptors, while monoclonal antibodies may target the extracellular binding sites (PubChem). Clinical use of these inhibitors is often associated with systemic side effects like hypertension and proteinuria due to the inhibition of physiological VEGF signaling in healthy tissues (PubMed: 23633442).

Other names

FLT1KDRFLK1Vascular endothelial growth factor receptor 1Vascular endothelial growth factor receptor 2VEGFR-1VEGFR-2Fms-like tyrosine kinase 1Kinase insert domain receptor

Inhibition of the intracellular tyrosine kinase domain to block downstream signaling pathways such as MAPK/ERK and PI3K/Akt, or competitive binding to the extracellular domain to prevent ligand-induced activation (PubMed: 24635023).