Back to discover

Protein / target

Vascular endothelial growth factor receptor 2

Encoded byKDRP35968Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
24
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Transmembrane receptor protein tyrosine kinase

Primary biology

EGFR/ERBB growth-factor signalling

Strongest disease association

Neoplasms

Via encoding gene KDR · Genetic evidence · score 0.28

Therapeutic position

Established drug target

Small molecules and antibodies

Research activity

Emerging research

5 papers · latest 2024

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD.

View complete UniProt function annotation

Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC

Subcellular location

Cell junctionEndoplasmic reticulumCell membraneCytoplasmNucleusCytoplasmic vesicleEarly endosomeSecreted
Domains and Gene Ontology detail (76)

Domains & features

Ig-like C2-type 1Ig-like C2-type 2Ig-like C2-type 3Ig-like C2-type 4Ig-like C2-type 5Ig-like C2-type 6Ig-like C2-type 7Protein kinase

Gene Ontology

  • Canchoring junction
  • Ccell junction
  • Ccytosol
  • Cearly endosome
  • Cendoplasmic reticulum
  • Cendosome
  • Cexternal side of plasma membrane
  • Cextracellular region
  • CGolgi apparatus
  • Cmembrane raft
  • Cnuclear membrane
  • Cplasma membrane

1356 aa · 152 kDa · 3 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell migrationGOGrowth-factor signallingGOReceptor tyrosine kinase signallingGOCell proliferation & survivalGOApoptosis & cell deathGO
View supporting evidence

Cell migration

  • ·cell migration
  • ·positive regulation of blood vessel endothelial cell migration
  • ·positive regulation of cell migration
  • ·positive regulation of cell migration involved in sprouting angiogenesis

Growth-factor signalling

  • ·growth factor binding
  • ·vascular endothelial growth factor binding
  • ·vascular endothelial growth factor receptor signaling pathway

Receptor tyrosine kinase signalling

  • ·transmembrane receptor protein tyrosine kinase activity
  • ·cell surface receptor protein tyrosine kinase signaling pathway

Cell proliferation & survival

  • ·positive regulation of cell population proliferation

Apoptosis & cell death

  • ·negative regulation of endothelial cell apoptotic process
  • ·negative regulation of neuron apoptotic process
View underlying pathways (7)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

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.

VEGFBCDH5NRP1VEGFCPGFVEGFDPECAM1FGF2SRCPDGFCKDR

10 strongest partners — larger node and heavier line mean higher confidence

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.

Approved medicines with mapped indications

5 medicines · 8 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Carcinoma, Renal Cell2 medicines
Colorectal Neoplasms2 medicines
Gastrointestinal Stromal Tumors1 medicine
Leukemia, Myeloid, Acute1 medicine
Mastocytosis1 medicine
Mastocytosis, Systemic1 medicine
Neuroendocrine Tumors1 medicine
Broader indication categories (1)

Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.

24 medicines meet Open Targets' target-level approved-medicine definition; the 5 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

7

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

sunitinib
ApprovedInhibitor

Vascular endothelial growth factor receptor 2 inhibitor

Indicated for Carcinoma, Renal Cell, Gastrointestinal Stromal Tumors, Neuroendocrine Tumors, Neoplasms

Direct interaction with this protein · 1 of 9 recorded protein targets — broad pharmacology

catequentinib
Phase 3Inhibitor

Vascular endothelial growth factor receptor 2 inhibitor

Direct interaction with this protein · 1 of 4 recorded protein targets

midostaurin
ApprovedInhibitor

Vascular endothelial growth factor receptor 2 inhibitor

Indicated for Leukemia, Myeloid, Acute, Mastocytosis, Mastocytosis, Systemic, Neoplasms

Direct interaction with this protein · 1 of 16 recorded protein targets — broad pharmacology

axitinib
ApprovedInhibitor

Vascular endothelial growth factor receptor inhibitor

Indicated for Carcinoma, Renal Cell, Neoplasms

Acts on a complex — shared with FLT1, FLT4 · 1 of 3 recorded protein targets — narrow recorded profile

regorafenib
ApprovedInhibitor

Vascular endothelial growth factor receptor inhibitor

Indicated for Colorectal Neoplasms, Neoplasms

Acts on a complex — shared with FLT1, FLT4 · 1 of 18 recorded protein targets — broad pharmacology

fruquintinib
ApprovedInhibitor

Vascular endothelial growth factor receptor inhibitor

Indicated for Colorectal Neoplasms, Neoplasms

Acts on a complex — shared with FLT1, FLT4 · 1 of 3 recorded protein targets — narrow recorded profile

View all 7 targeting drugs
Semaxanib
Phase 3Inhibitor

Vascular endothelial growth factor receptor inhibitor

Acts on a complex — shared with FLT1, FLT4 · 1 of 4 recorded protein targets

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene KDR

Gene-level evidence surfaced through the gene KDRthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Neoplasms
0.92Well supported

Clinical evidence dominant · Open Targets 0.68

Carcinoma, Hepatocellular
0.84Well supported

Clinical evidence dominant · Open Targets 0.68

Gastrointestinal Stromal Tumors
0.82Well supported

Clinical evidence dominant · Open Targets 0.66

Carcinoma, Non-Small-Cell Lung
0.82Well supported

Clinical evidence dominant · Open Targets 0.65

Carcinoma, Renal Cell
0.81Well supported

Clinical evidence dominant · Open Targets 0.66

View evidence synthesis (5)
NeoplasmsWell supported
0.92
agreement 0.831.00
Clinical42%Somatic mutation17%Pathway17%Genetic16%Literature9%

Open Targets aggregate 0.68 · 5 independent evidence families

Carcinoma, HepatocellularWell supported
0.84
agreement 0.720.96
Clinical63%Somatic mutation25%Literature12%

Open Targets aggregate 0.68 · 3 independent evidence families

Gastrointestinal Stromal TumorsWell supported
0.82
agreement 0.700.94
Clinical64%Somatic mutation27%Literature9%

Open Targets aggregate 0.66 · 3 independent evidence families

Carcinoma, Non-Small-Cell LungWell supported
0.82
agreement 0.710.93
Clinical60%Somatic mutation26%Literature12%RNA expression2%

Open Targets aggregate 0.65 · 4 independent evidence families

Carcinoma, Renal CellWell supported
0.81
agreement 0.690.93
Clinical72%Somatic mutation19%Literature9%

Open Targets aggregate 0.66 · 3 independent evidence families

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 per-type scores above show the calculation.

Show all associations
Neoplasms0.68
Carcinoma, Hepatocellular0.68
Gastrointestinal Stromal Tumors0.66
Carcinoma, Renal Cell0.66
Carcinoma, Non-Small-Cell Lung0.65
Gastric adenocarcinoma0.64
Leukemia, Myeloid, Acute0.63
Thyroid gland carcinoma0.63
Colorectal Neoplasms0.60

Drug development

75 compounds recorded · 24 approved · 49 in clinical development · 2 earlier-stage

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 7 drugs that target this protein in Forefront's canonical graph (5 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
XL-820Phase 2
VATALANIBPhase 3
RIVOCERANIB MESYLATEApproval
4SC-203Phase 1
LINIFANIBPhase 3
OLINVACIMABPhase 2
XL-999Phase 2
LENVATINIBApproval
TELBERMINPhase 2
FAMITINIBPhase 3

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesStrong

Approved Drug and UniProt loc high conf support this modality.

Protein degradersEmerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Advanced Clinical support this modality.

View underlying tractability evidence (14)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · Approved DrugAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

Increased, Developmental DefectsAOP-Wikidrug toxicityClinPGxheart diseaseForce et al. (2011)rashBrennan et al. (2024)Hypertension and hand-foot skin reactionsClinPGxaneurysmBrennan et al. (2024)haemorrhageBrennan et al. (2024)myocardial hypoperfusionBrennan et al. (2024)nauseaBrennan et al. (2024)vomitingBrennan et al. (2024)decreased appetiteBrennan et al. (2024)regulation of catalytic activityToxCast

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

RECRUITING · via catequentinib · NCT06970145

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 5 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. New publication2026-01-28
    Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial.

    Nature medicine · 2026 · 8 citations · Europe PMC · via axitinib

  2. Regulatory approval2024-09-19

    Approval: Axitinib Accord (EMA)

    ema · regulatory · ema · via axitinib

  3. Regulatory approval2024-06-20

    Approval: Fruzaqla (EMA)

    ema · regulatory · ema · via fruquintinib

  4. New publication2024-06-04
    Lenvatinib Plus Pembrolizumab Versus Standard of Care for Previously Treated Metastatic Colorectal Cancer: Final Analysis of the Randomized, Open-Label, Phase III LEAP-017 Study.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024 · 69 citations · Europe PMC · via regorafenib

  5. New publication2024-05-03
    Machine-learning and mechanistic modeling of metastatic breast cancer after neoadjuvant treatment.

    PLoS computational biology · 2024 · 10 citations · Europe PMC · via sunitinib

  6. New publication2024-03-15
    The more the merrier? Evidence and efficacy of immune checkpoint- and tyrosine kinase inhibitor combinations in advanced solid cancers.

    Cancer treatment reviews · 2024 · 17 citations · Europe PMC · via axitinib

  7. New publication2024-01-05
    Genomic profiling in GIST: Implications in clinical outcome and future challenges.

    Neoplasia (New York, N.Y.) · 2024 · 20 citations · Europe PMC · via sunitinib

  8. Regulatory approval2021-02-11

    Approval: Sunitinib Accord (EMA)

    ema · regulatory · ema · via sunitinib

  9. Regulatory approval2017-09-18

    Approval: Rydapt (EMA)

    ema · regulatory · ema · via midostaurin

  10. Regulatory approval2013-08-26

    Approval: Stivarga (EMA)

    ema · regulatory · ema · via regorafenib

  11. Regulatory approval2012-09-03

    Approval: Inlyta (EMA)

    ema · regulatory · ema · via axitinib

  12. Regulatory approval2006-07-19

    Approval: Sutent (EMA)

    ema · regulatory · ema · via sunitinib

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.

Research activity

5 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Recent

Europe PMC papers linked directly to this protein.