VEGF receptors are homo- and heterodimeric proteins, which are characterized by seven Ig-like loops in their extracellular domains and a split kinase domain in the cytoplasmic region. They are key regulators of angiogenesis and lymphangiogenesis; as such, they have been the focus of drug discovery for conditions such as metastatic cancer. Splice variants of VEGFR1 and VEGFR2 generate truncated proteins limited to the extracellular domains, capable of homodimerisation and binding VEGF ligands as a soluble, non-signalling entity. Ligands at VEGF receptors are typically homodimeric. VEGFA (VEGFA, P15692) is able to activate VEGFR1 homodimers, VEGFR1/2 heterodimers and VEGFR2/3 heterodimers. VEGFB (VEGFB, P49765) and placental growth factor (PGF, P49763) activate VEGFR1 homodimers, while VEGFC (VEGFC, P49767) and VEGFD (VEGFD, O43915) activate VEGFR2/3 heterodimers and VEGFR3 homodimers, and, following proteolysis, VEGFR2 homodimers.

The VEGFR, as well as VEGF ligands, have been targeted by antibodies and tyrosine kinase inhibitors. DMH4 [4], Ki8751 [10] and ZM323881, a novel inhibitor of vascular endothelial growth factor-receptor-2 tyrosine kinase activity [15] are described as VEGFR2-selective tyrosine kinase inhibitors. Bevacizumab is a monoclonal antibody directed against VEGF-A, used clinically for the treatment of certain metastatic cancers; an antibody fragment has been used for wet age-related macular degeneration.

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