Protein / target
Vascular endothelial growth factor receptor 1
Protein at a glance
Biological role
Transmembrane receptor protein tyrosine kinase activity
Primary system
Cardiovascular system
Strongest disease association
coronary artery disorder
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
18 approved · 29 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. Acts as a positive regulator of postnatal retinal hyaloid vessel regression (By similarity). May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1 (PubMed:16685275)
Subcellular location
Domains and Gene Ontology detail (38)Hide
Domains & features
Gene Ontology
- Cendosome
- Cextracellular space
- Cfocal adhesion
- Cplasma membrane
- Creceptor complex
- FATP binding
- Fgrowth factor binding
- Fplacental growth factor receptor activity
- Ftransmembrane receptor protein tyrosine kinase activity
- Fvascular endothelial growth factor receptor activity
- Pblood vessel morphogenesis
- Pcell differentiation
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Kinase signalling
- ·Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, a…
- ·transmembrane receptor protein tyrosine kinase activity
- ·peptidyl-tyrosine phosphorylation
- ·positive regulation of MAP kinase activity
View underlying pathways (2)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Vascular endothelial growth factor receptor 1 inhibitor
Appears in clinical studies involving gastrointestinal stromal tumor, renal cell carcinoma, gastrointestinal stromal tumor, neuroendocrine neoplasm
Vascular endothelial growth factor receptor inhibitor
Appears in clinical studies involving renal cell carcinoma, renal cell carcinoma, neoplasm, pancreatic adenocarcinoma
Vascular endothelial growth factor receptor inhibitor
Appears in clinical studies involving colorectal cancer, metastatic colorectal cancer, colorectal neoplasm, neoplasm
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 1,212 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 48 total
soft tissue sarcoma · renal cell carcinoma · sarcoma
small cell lung carcinoma · breast cancer · lung cancer
small cell lung carcinoma · cancer · ovarian cancer
diabetic foot · lateral sclerosis · amyotrophic lateral sclerosis
renal cell carcinoma · neoplasm · renal cell carcinoma
hepatocellular carcinoma · colorectal carcinoma · lung cancer
renal cell carcinoma · neoplasm · renal cell adenocarcinoma
hepatocellular carcinoma · renal cell carcinoma · non-small cell lung carcinoma
non-small cell lung carcinoma · non-small cell lung carcinoma · cancer
Tractability
Safety liabilities
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 3 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- New publicationFecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial.
- New publicationEfficacy of pembrolizumab in microsatellite-stable, tumor mutational burden-high metastatic colorectal cancer: genomic signatures and clinical outcomes.
- Regulatory approval
Approval: Axitinib Accord (EMA)
- New publicationLenvatinib Plus Pembrolizumab Versus Standard of Care for Previously Treated Metastatic Colorectal Cancer: Final Analysis of the Randomized, Open-Label, Phase III LEAP-017 Study.
- New publicationMachine-learning and mechanistic modeling of metastatic breast cancer after neoadjuvant treatment.
- New publicationThe more the merrier? Evidence and efficacy of immune checkpoint- and tyrosine kinase inhibitor combinations in advanced solid cancers.
- New publicationGenomic profiling in GIST: Implications in clinical outcome and future challenges.
- New publicationNivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma.
- Regulatory approval
Approval: Sunitinib Accord (EMA)
- New publicationTargeted therapy for hepatocellular carcinoma.
- New publicationLiver transarterial chemoembolization and sunitinib for unresectable hepatocellular carcinoma: Results of the PRODIGE 16 study.
- New publicationUpdated efficacy results from the JAVELIN Renal 101 trial: first-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.