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Protein / target

Vascular endothelial growth factor receptor 3

Encoded byFLT4P35916Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
18
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

Strongest disease association

Lymphatic malformation 1

Via encoding gene FLT4 · Genetic evidence · score 0.95

Therapeutic position

Established drug target

Small molecules and antibodies

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 VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development.

View complete UniProt function annotation

Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr-185', and of AKT1 at 'Ser-473'

Subcellular location

Cell membraneCytoplasmNucleusSecreted
Domains and Gene Ontology detail (42)

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

  • Ccytosol
  • Cextracellular region
  • Cnucleus
  • Cplasma membrane
  • Creceptor complex
  • FATP binding
  • Fgrowth factor binding
  • Fprotein homodimerization activity
  • Fprotein phosphatase binding
  • Ftransmembrane receptor protein tyrosine kinase activity
  • Fvascular endothelial growth factor receptor activity
  • Pblood vessel morphogenesis

1363 aa · 153 kDa · 3 isoforms

Biological roles

Reactome v97

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

Cell migrationGOReceptor tyrosine kinase signallingGOGrowth-factor signallingGOCell proliferation & survivalGO
View supporting evidence

Cell migration

  • ·cell migration
  • ·positive regulation of cell migration
  • ·positive regulation of endothelial cell migration

Receptor tyrosine kinase signalling

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

Growth-factor signalling

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

Cell proliferation & survival

  • ·positive regulation of cell population proliferation
View underlying pathways (3)

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.

VEGFCVEGFBVEGFDPGFKDRNRP2PDGFCANGPT2GRB2SHC1FLT4

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

4 medicines · 5 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
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.

18 medicines meet Open Targets' target-level approved-medicine definition; the 4 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

6

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 3 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 3 inhibitor

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

axitinib
ApprovedInhibitor

Vascular endothelial growth factor receptor inhibitor

Indicated for Carcinoma, Renal Cell, Neoplasms

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

Semaxanib
Phase 3Inhibitor

Vascular endothelial growth factor receptor inhibitor

Acts on a complex — shared with FLT1, KDR · 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 FLT4

Gene-level evidence surfaced through the gene FLT4that 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.

Lymphatic malformation 1
0.96Well supported

Genetic evidence dominant · Open Targets 0.78

Congenital heart defects, multiple types, 7
0.93Well supported

Genetic evidence dominant · Open Targets 0.77

Milroy disease
0.89Well supported

Genetic evidence dominant · Open Targets 0.75

Capillary infantile hemangioma
0.86Well supported

Genetic evidence dominant · Open Targets 0.63

Carcinoma, Non-Small-Cell Lung
0.82Well supported

Clinical evidence dominant · Open Targets 0.64

View evidence synthesis (5)
Lymphatic malformation 1Well supported
0.96
agreement 0.841.00
Genetic82%Animal model17%Literature1%Genetic literaturedup

Open Targets aggregate 0.78 · 3 independent evidence families · 1 not counted as duplicate

Congenital heart defects, multiple types, 7Well supported
0.93
agreement 0.821.00
Genetic71%Somatic mutation28%Literature0%Genetic literaturedup

Open Targets aggregate 0.77 · 3 independent evidence families · 1 not counted as duplicate

Milroy diseaseWell supported
0.89
agreement 0.771.00
Genetic75%Animal model21%Literature4%Genetic literaturedup

Open Targets aggregate 0.75 · 3 independent evidence families · 1 not counted as duplicate

Capillary infantile hemangiomaWell supported
0.86
agreement 0.760.96
Genetic55%Somatic mutation27%Animal model18%Genetic literaturedup

Open Targets aggregate 0.63 · 3 independent evidence families · 1 not counted as duplicate

Carcinoma, Non-Small-Cell LungWell supported
0.82
agreement 0.700.94
Clinical58%Somatic mutation34%Literature8%

Open Targets aggregate 0.64 · 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
Lymphatic malformation 10.78
Congenital heart defects, multiple types, 70.77
Milroy disease0.75
Carcinoma, Hepatocellular0.68
Gastrointestinal Stromal Tumors0.65
Carcinoma, Non-Small-Cell Lung0.64
Capillary infantile hemangioma0.63
Neoplasms0.62
Carcinoma, Renal Cell0.61
Thyroid gland carcinoma0.60

Drug development

47 compounds recorded · 18 approved · 28 in clinical development · 1 earlier-stage

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 6 drugs that target this protein in Forefront's canonical graph (4 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
OSI-930Phase 1
TIVOZANIBApproval
JNJ-26483327Phase 1
CATEQUENTINIBPhase 3
IBCASERTIBPhase 3
TELATINIBPhase 2
SUNITINIBApproval
XL-820Phase 2
BRIVANIBPhase 3
SORAFENIBApproval

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 High-Quality Ligand support this modality.

AntibodiesSupported

Phase 1 Clinical and UniProt loc high conf support this modality.

Protein degradersEmerging

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

View underlying tractability evidence (10)
SM · Approved DrugSM · High-Quality LigandSM · Druggable FamilyAB · Phase 1 ClinicalAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

regulation of catalytic activityToxCastheart diseaseForce et al. (2011)

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 4 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. New publication2021-03-01
    Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma.

    The New England journal of medicine · 2021 · 1,297 citations · Europe PMC · via sunitinib

  9. Regulatory approval2021-02-11

    Approval: Sunitinib Accord (EMA)

    ema · regulatory · ema · via sunitinib

  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.