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Protein / target

Vascular endothelial growth factor receptor 1

Encoded byFLT1P17948Homo 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

Primary biology

EGFR/ERBB growth-factor signalling

Strongest disease association

Coronary Artery Disease

Via encoding gene FLT1 · Genetic evidence · score 0.93

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 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.

View complete UniProt function annotation

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

Cell membraneEndosomeSecretedCytoplasm
Domains and Gene Ontology detail (38)

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

  • 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

1338 aa · 151 kDa · 8 isoforms

Biological roles

Reactome v97

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

Cell migrationUniProt · GOCell proliferation & survivalUniProt · GOReceptor tyrosine kinase signallingGOGrowth-factor signallingGO
View supporting evidence

Cell migration

  • ·Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, a…
  • ·cell migration
  • ·monocyte chemotaxis
  • ·positive regulation of cell migration

Cell proliferation & survival

  • ·Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, a…
  • ·positive regulation of cell population proliferation

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
View underlying pathways (2)

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.

VEGFCVEGFBPGFVEGFDKDRNRP1FGF2PDGFCANGPT1ANGPT2FLT1

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

5

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 1 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

axitinib
ApprovedInhibitor

Vascular endothelial growth factor receptor inhibitor

Indicated for Carcinoma, Renal Cell, Neoplasms

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

Gene-level evidence surfaced through the gene FLT1that 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.

Coronary Artery Disease
0.94Well supported

Genetic evidence dominant · Open Targets 0.57

Carcinoma, Renal Cell
0.76Well supported

Clinical evidence dominant · Open Targets 0.61

Neoplasms
0.76Well supported

Clinical evidence dominant · Open Targets 0.61

Carcinoma, Hepatocellular
0.76Well supported

Clinical evidence dominant · Open Targets 0.61

Colorectal Neoplasms
0.73Moderately supported

Clinical evidence dominant · Open Targets 0.60

View evidence synthesis (5)
Coronary Artery DiseaseWell supported
0.94
agreement 0.801.00
Genetic97%Literature3%

Open Targets aggregate 0.57 · 2 independent evidence families

Carcinoma, Renal CellWell supported
0.76
agreement 0.600.91
Clinical93%Literature7%

Open Targets aggregate 0.61 · 2 independent evidence families

NeoplasmsWell supported
0.76
agreement 0.600.91
Clinical83%Literature17%

Open Targets aggregate 0.61 · 2 independent evidence families

Carcinoma, HepatocellularWell supported
0.76
agreement 0.600.91
Clinical89%Literature11%

Open Targets aggregate 0.61 · 2 independent evidence families

Colorectal NeoplasmsModerately supported
0.73
agreement 0.580.89
Clinical95%Literature5%

Open Targets aggregate 0.60 · 2 independent evidence families

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 per-type scores above show the calculation.

Show all associations
Carcinoma, Renal Cell0.61
Neoplasms0.61
Carcinoma, Hepatocellular0.61
Colorectal Neoplasms0.60
Idiopathic Pulmonary Fibrosis0.59
Gastrointestinal Stromal Tumors0.59
Coronary Artery Disease0.57
Carcinoma, Non-Small-Cell Lung0.56
Medullary thyroid gland carcinoma0.55

Drug development

48 compounds recorded · 18 approved · 29 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 5 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)
PAZOPANIB HYDROCHLORIDEApproval
LUCITANIBPhase 3
4SC-203Phase 1
IBCASERTIBPhase 3
TELBERMINPhase 2
PAZOPANIBApproval
BRIVANIB ALANINATEPhase 3
TIVOZANIBApproval
LINIFANIBPhase 3
GLESATINIBPhase 2

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

Advanced Clinical and UniProt loc high conf support this modality.

Protein degradersEmerging

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

Other modalitiesStrong

Advanced Clinical support this modality.

View underlying tractability evidence (15)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · Advanced ClinicalAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · LiteraturePR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

brain natriuretic peptide increaseBrennan et al. (2024)Increased, Developmental DefectsAOP-WikihyponatraemiaBrennan et al. (2024)impaired healingBrennan et al. (2024)heart diseaseForce et al. (2011)HaemorrhageBrennan et al. (2024)regulation of catalytic activityToxCasthypertensionBrennan et al. (2024)

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)

ACTIVE_NOT_RECRUITING · via regorafenib · NCT05395741

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.