Target intelligence / Profile preview

Vascular endothelial growth factor receptor 2 (VEGFR-2) (VEGFR-2 (also KDR in human; Flk-1 in mouse))

Target
VEGFR-2 (also KDR in human; Flk-1 in mouse)
Molecular classification
Receptor, Receptor tyrosine kinase (RTK)
01

Overview

Vascular endothelial growth factor receptor 2 is a type III receptor tyrosine kinase expressed predominantly on vascular endothelial cells that mediates most of the prototypical responses to VEGF-A, including endothelial proliferation, migration, survival, vascular permeability, and nitric oxide production, by autophosphorylation at key tyrosines (e.g., Y951, Y1054/Y1059, Y1175, Y1214) and activation of downstream pathways such as PI3K/AKT/mTOR, Ras/Raf/MEK/ERK, and p38 MAPK; it is central to physiological vasculogenesis and angiogenesis and is pathologically upregulated or activated in cancers and other diseases, making it a major therapeutic target for anti-angiogenic agents including anti-VEGF antibodies, ligand traps, and VEGFR tyrosine kinase inhibitors

Other names
Kinase insert domain receptor (KDR)Fetal liver kinase-1 (Flk-1, mouse ortholog)VEGF receptor 2VEGFR2
02

Mechanism of action

Ligand neutralization (anti-VEGF-A antibodies prevent VEGF from binding VEGFRs); Decoy receptor/ligand trap (aflibercept binds VEGF-A and related ligands, preventing receptor activation); Tyrosine kinase inhibition (ATP-competitive inhibition of VEGFR-2 kinase activity to block downstream signaling)

03

Biological functions

Angiogenesis (endothelial proliferation, migration, survival)VasculogenesisVascular permeability regulationSignal transduction via PI3K/AKT, Ras/Raf/MEK/ERK, p38 MAPK pathwaysNitric oxide production and endothelial function (via eNOS)Lymphangiogenesis is primarily via VEGFR-3 but VEGF-A/VEGFR-2 contributes to angiogenesis
04

Disease associations

Cancer (tumor angiogenesis, growth, metastasis)Ocular disorders (neovascular age-related macular degeneration, diabetic macular edema)Cardiovascular disease and ischemic disease (insufficient or excessive signaling implicated)Inflammation and wound healing abnormalitiesPotential roles in neurovascular pathology and blood–brain barrier permeability changes
05

Safety considerations

Hypertension (including grade 3–4)Hemorrhage/bleeding eventsThromboembolic eventsGastrointestinal perforation (noted with bevacizumab)Impaired wound healing and increased vascular permeability; resistance and suboptimal efficacy in tumors are common therapeutic challenges
06

Interacting drugs

Monoclonal antibodies/ligand traps: Bevacizumab (anti-VEGF-A)

2 more in the full profile.

07

Biomarkers

VEGF-A levels as a pathway activity marker and pharmacodynamic readoutTumor or endothelial VEGFR-2 expression/activation (p-VEGFR-2)Imaging or fluid biomarkers of angiogenesis/permeability (e.g., retinal thickness/vascular leakage in ocular disease; not specific but commonly used clinically)

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