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Protein / target

Integrin alpha-4

Encoded byITGA4P13612Homo sapiensSwiss-Prot
UniProt: P13612Ensembl: ENSG00000115232HGNC: HGNC:6140NCBI Gene: 3676
Clinically validated
Therapeutic maturity
2
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Advanced Clinical

Protein at a glance

Biological role

Cell adhesion molecule binding

Strongest disease association

Inflammatory Bowel Diseases

Via encoding gene ITGA4 · Genetic evidence · score 0.84

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

Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin.

View complete UniProt function annotation

Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are also receptors for VCAM1. Integrin alpha-4/beta-1 recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-4/beta-7 is also a receptor for MADCAM1. It recognizes the sequence L-D-T in MADCAM1. On activated endothelial cells integrin VLA-4 triggers homotypic aggregation for most VLA-4-positive leukocyte cell lines. It may also participate in cytolytic T-cell interactions with target cells. ITGA4:ITGB1 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling (PubMed:23125415). ITGA4:ITGB1 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877). Integrin ITGA4:ITGB1 represses PRKCA-mediated L-type voltage-gated channel Ca(2+) influx and ROCK-mediated calcium sensitivity in vascular smooth muscle cells via its interaction with SVEP1, thereby inhibiting vasocontraction (PubMed:35802072)

Subcellular location

Membrane
Domains and Gene Ontology detail (40)

Gene Ontology

  • Ccell surface
  • Cextracellular exosome
  • Cfocal adhesion
  • Cgrowth cone
  • Cintegrin alpha4-beta1 complex
  • Cintegrin alpha4-beta7 complex
  • Cmembrane
  • Cneuronal cell body
  • Cplasma membrane
  • Fcell adhesion molecule binding
  • Fcoreceptor activity
  • Ffibronectin binding

1032 aa · 115 kDa · 2 isoforms

Biological roles

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

Cell migrationGOIon channel gatingUniProtImmune signallingGOCell adhesionGO
View supporting evidence

Cell migration

  • ·cell-matrix adhesion involved in ameboidal cell migration
  • ·positive regulation of T cell migration

Ion channel gating

  • ·Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They…

Immune signalling

  • ·protein antigen binding
  • ·B cell differentiation
  • ·cellular response to cytokine stimulus
  • ·immune response in gut-associated lymphoid tissue

Cell adhesion

  • ·cell adhesion molecule binding
  • ·cell-cell adhesion
  • ·cell-cell adhesion mediated by integrin
  • ·heterotypic cell-cell adhesion

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

Approved medicines with mapped indications

2 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.

Crohn's Disease2 medicines
natalizumabvedolizumab
Colitis, Ulcerative1 medicine
vedolizumab
Inflammation1 medicine
natalizumab
Multiple Sclerosis1 medicine
natalizumab
Multiple Sclerosis, Relapsing-Remitting1 medicine
natalizumab

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

2

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.

natalizumab
ApprovedInhibitor

Integrin alpha-4/beta-7 inhibitor

Indicated for Crohn's Disease, Inflammation, Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting

Acts on a complex — shared with ITGB7 · 1 of 3 recorded protein targets — narrow recorded profile

vedolizumab
ApprovedInhibitor

Integrin alpha-4/beta-7 inhibitor

Indicated for Colitis, Ulcerative, Crohn's Disease

Acts on a complex — shared with ITGB7 · 1 of 2 recorded protein targets — narrow recorded profile

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 ITGA4

Gene-level evidence surfaced through the gene ITGA4 that 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.

Crohn's Disease
0.95Well supported

Genetic evidence dominant · Open Targets 0.72

Inflammatory Bowel Diseases
0.90Well supported

Genetic evidence dominant · Open Targets 0.58

Colitis, Ulcerative
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

Multiple Sclerosis
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

Hypothyroidism
0.68Moderately supported

Genetic evidence dominant · Open Targets 0.41

View evidence synthesis (5)
Crohn's DiseaseWell supported
0.95
agreement 0.84–1.00
Genetic52%Clinical47%Literature1%

Open Targets aggregate 0.72 · 3 independent evidence families

Inflammatory Bowel DiseasesWell supported
0.90
agreement 0.79–1.00
Genetic71%Clinical27%Literature2%

Open Targets aggregate 0.58 · 3 independent evidence families

Colitis, UlcerativeModerately supported
0.74
agreement 0.61–0.88
Clinical97%Literature3%RNA expression0%

Open Targets aggregate 0.60 · 3 independent evidence families

Multiple SclerosisModerately supported
0.74
agreement 0.58–0.90
Clinical97%Literature3%

Open Targets aggregate 0.60 · 2 independent evidence families

HypothyroidismModerately supported
0.68
agreement 0.56–0.80
Genetic100%

Open Targets aggregate 0.41 · 1 independent evidence family

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
Crohn's Disease0.72
Colitis, Ulcerative0.60
Multiple Sclerosis0.60
Inflammatory Bowel Diseases0.58
Neurodegenerative Diseases0.45
Hypothyroidism0.41
Multiple Sclerosis, Relapsing-Remitting0.38

Drug development

5 compounds recorded · 2 approved · 3 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (5)
NATALIZUMABApproval
FIRATEGRASTPhase 2
VEDOLIZUMABApproval
ABRILUMABPhase 2
UCB-1184197Phase 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 molecules — Strong

Advanced Clinical and Structure with Ligand support this modality.

Antibodies — Strong

Approved Drug and GO CC high conf support this modality.

Protein degraders — Emerging

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

View underlying tractability evidence (11)
SM · Advanced ClinicalSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · Approved DrugAB · GO CC high confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

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.

CURVE-UC: A Pragmatic Randomized, Double-blind, Placebo Controlled, Treat-through, Multi-site Pragmatic Interventional Study to Evaluate the Efficacy and Safety of Combination Curcumin-QingDai (CurQD) With Vedolizumab in Moderate to Severe Ulcerative Colitis (UC)PHASE4

NOT_YET_RECRUITING · via vedolizumab · NCT07665294

A Prospective, Multicenter, Interventional, Open-Label, Single-arm Phase IV Study Over 24 Weeks to Investigate the Radiological Onset of Action After Treatment Initiation With Subcutaneous Natalizumab in Patients With Relapsing-Remitting Multiple Sclerosis (TYS-ON)PHASE4

TERMINATED · via natalizumab · NCT05532163

A Phase 4 Study Evaluating Moderate to Severely Active Ulcerative Colitis or Crohn's Disease and the Use of Vedolizumab Subcutaneous Within a Community SettingPHASE4

RECRUITING · via vedolizumab · NCT06581328

Comparison of Vedolizumab Treatment to Adalimumab Dose Intensification in Crohn's Disease Patients With Loss of Response or Biomarker Activity to Adalimumab on First Line With Therapeutic Drug Concentration: A Randomized, Multicentre, Controlled TrialPHASE4

RECRUITING · via vedolizumab · NCT06180382

View all trials (26)
A Multicenter Randomized, Double-blind, Placebo-controlled Study on the Efficacy and Safety of Combining Probiotic VSL#3 With Vedolizumab for the Treatment of Moderate Ulcerative ColitisPHASE4

RECRUITING · via vedolizumab · NCT06609447

An Interventional Study to Evaluate Treating to a Target of Transmural Healing in Patients With Moderately to Severely Active Crohn's DiseasePHASE4

RECRUITING · via vedolizumab · NCT06257706

An Open-Label, Phase 4, Single-Arm, Multicenter Study to Evaluate the Induction of Response and Remission of Vedolizumab Dual Targeted Therapy With Tofacitinib in Adult Patients With Moderately to Severely Active Ulcerative ColitisPHASE4

RECRUITING · via vedolizumab · NCT06095128

An Open-Label, Phase 4 Study to Evaluate the Efficacy and Safety of Dual Targeted Therapy With Vedolizumab Intravenous (IV) and Adalimumab Subcutaneous (SC) or Vedolizumab IV and Ustekinumab IV/SC in Moderate to Severe Crohn's Disease (CD)PHASE4

RECRUITING · via vedolizumab · NCT06045754

Subcutaneous Vedolizumab Drug De-escalation Using Therapeutic Drug Monitoring in Inflammatory Bowel Disease: a Randomized Controlled Pilot StudyPHASE4

RECRUITING · via vedolizumab · NCT06584162

Changes in Intestinal Microecology Before and After Vedolizumab Treatment for Ulcerative Colitis and Correlation With EfficacyPHASE4

RECRUITING · via vedolizumab · NCT05481619

Phase 3b, Multicenter, Randomized, Open-Label Study of Risankizumab Compared to Vedolizumab for the Treatment of Adult Subjects With Moderate to Severe Ulcerative Colitis Who Are Naïve to Targeted TherapiesPHASE3

ACTIVE_NOT_RECRUITING · via vedolizumab · NCT06880744

An Open-Label, Phase 3 Study to Evaluate the Pharmacokinetics, Safety, and Immunogenicity of Vedolizumab Subcutaneous in Pediatric Subjects With Moderately to Severely Active Ulcerative Colitis or Crohn's Disease Who Achieved Clinical Response Following Open-Label Vedolizumab Intravenous TherapyPHASE3

RECRUITING · via vedolizumab · NCT06100289

A Randomized, Double-Blind, Phase 3b Study to Evaluate the Short- and Long-Term Efficacy and Safety of Dual Targeted Therapy With Intravenous Vedolizumab and Oral Upadacitinib Compared With Intravenous Vedolizumab and Oral Placebo for Induction Followed by Intravenous Vedolizumab Monotherapy for Maintenance in the Treatment of Adults With Moderately to Severely Active Crohn's DiseasePHASE3

RECRUITING · via vedolizumab · NCT06227910

An Open-label Single-Arm Phase 3 Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Vedolizumab Intravenous in the Treatment of Pediatric Subjects With Active Chronic PouchitisPHASE3

RECRUITING · via vedolizumab · NCT06443502

VERIFY: Vedolizumab for the Prevention of Immune Checkpoint Inhibitor Related Diarrhea or Colitis in Patients With Cancer: A Randomized, Double-Blinded, Placebo Controlled TrialPHASE2/PHASE3

NOT_YET_RECRUITING · via vedolizumab · NCT06337695

A Phase 3, Multicenter, Randomized, Parallel-Group, Double-blind, Placebo-Controlled Induction Study Followed by an Open-label Extension Period to Evaluate the Efficacy and Safety of Intravenous Vedolizumab (300 mg) Infusion Treatment in Subjects in China With Moderately to Severely Active Crohn's DiseasePHASE3

RECRUITING · via vedolizumab · NCT05837897

A Phase 3b Extension Study to Evaluate the Long-term Safety of Vedolizumab Intravenous in Pediatric Patients With Ulcerative Colitis or Crohn's DiseasePHASE3

RECRUITING · via vedolizumab · NCT05442567

A Randomized, Double-Blind, Phase 3 Study to Evaluate the Efficacy and Safety of Vedolizumab Intravenous as Maintenance Therapy in Pediatric Subjects With Moderately to Severely Active Crohn's Disease Who Achieved Clinical Response Following Open-Label Vedolizumab Intravenous TherapyPHASE3

RECRUITING · via vedolizumab · NCT04779320

An Open-Label, Phase 3 Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Intravenous (IV) Vedolizumab Administered Every 4 Weeks (Q4W) in Japanese Patients With Moderate to Severe Ulcerative Colitis or Crohn's Disease Who Experienced Secondary Loss of Response During Maintenance Therapy With Vedolizumab IV Administered Every 8 Weeks (Q8W)PHASE3

ACTIVE_NOT_RECRUITING · via vedolizumab · NCT04738942

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Examine the Efficacy and Safety of Intravenous Vedolizumab (300 mg) Infusion Treatment in Chinese Subjects With Moderately to Severely Active Ulcerative ColitisPHASE3

ACTIVE_NOT_RECRUITING · via vedolizumab · NCT03221036

PHOENIX- A Phase 2, Randomized, Controlled, Open-label, Multicenter Study to Evaluate the Efficacy and Safety/Tolerability of Extracorporeal Photopheresis (ECP) Versus Best Available Therapy (BAT) for the Treatment of Immune-related Colitis or Hepatitis With Inadequate Response to Corticosteroids in Participants With Unresectable or Metastatic Melanoma Treated With Immune Checkpoint Inhibitors (ICI)PHASE2

NOT_YET_RECRUITING · via vedolizumab · NCT07619898

Early Concomitant Vedolizumab as First-Line for Immune-Related Colitis Therapy TrialPHASE2

RECRUITING · via vedolizumab · NCT06841705

A Phase 2a, Two-Part, Open-Label and Randomized Study to Evaluate the Safety and Efficacy of OD-07656 and of Subsequent Vedolizumab Therapy in Patients With Moderately to Severely Active Ulcerative ColitisPHASE2

RECRUITING · via vedolizumab · NCT06850727

Phase-2 Study of Vedolizumab Plus Post-Transplant Cyclophosphamide and Short Course Tacrolimus for Graft-versus-Host Disease Prevention After Reduced Intensity Conditioning Peripheral Blood Stem Cell Allogeneic Hematopoietic Cell TransplantationPHASE2

RECRUITING · via vedolizumab · NCT06815003

Vedolizumab for the Treatment of Collagenous GastritisPHASE2

ACTIVE_NOT_RECRUITING · via vedolizumab · NCT06317220

Treatment of Immune Checkpoint Inhibitor-Related Colitis With Infliximab or Vedolizumab: A Randomized TrialPHASE1/PHASE2

ACTIVE_NOT_RECRUITING · via vedolizumab · NCT04407247

Maintenance in Autologous Stem Cell Transplant for Crohn's Disease (MASCT - CD)PHASE2

RECRUITING · via vedolizumab · NCT03219359

Role of Microbiome in the Realm of Immune-Checkpoint Inhibitor Induced GI Complications In Cancer PopulationPHASE1

RECRUITING · via vedolizumab · NCT03819296

Efficacy and Safety Analysis of Sequential Treatment of Moderate to Severe Ulcerative Colitis With Vedolizumab and Upadacitinib: A Multicenter Prospective Randomized Controlled Clinical StudyNA

RECRUITING · via vedolizumab · NCT06095596

Mirikizumab Therapy is Effective for Patients With Moderate to Severe Ulcerative Colitis Patients Whose Geboes Score Grade is ≥3.2) on Endoscopic BiopsyPHASE4

COMPLETED · via vedolizumab · NCT06626165

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 2 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. Supplemental approval2026-07-23

    Supplemental approval: NATALIZUMAB-SZTN (BLA761322)

    fda · regulatory · fda · via natalizumab

  2. Supplemental approval2026-02-02

    Supplemental approval: NATALIZUMAB-SZTN (BLA761322)

    fda · regulatory · fda · via natalizumab

  3. Label change2025-10-30

    Label change: NATALIZUMAB-SZTN (BLA761322)

    fda · regulatory · fda · via natalizumab

  4. Regulatory approval2023-09-22

    Approval: Tyruko (EMA)

    ema · regulatory · ema · via natalizumab

  5. Regulatory approval2023-08-24

    Approval: NATALIZUMAB-SZTN (BLA761322)

    fda · regulatory · fda · via natalizumab

  6. New publication2019-02-26
    Vedolizumab in Japanese patients with ulcerative colitis: A Phase 3, randomized, double-blind, placebo-controlled study.

    PloS one · 2019 · 78 citations · Europe PMC · via vedolizumab

  7. Safety communication2016-04-18

    Drug Safety Update: Natalizumab (Tysabri▼): progressive multifocal leukoencephalopathy—updated advice to support early detection

    mhra · safety · mhra · via natalizumab

  8. Safety communication2014-12-11

    Drug Safety Update: Natalizumab (Tysabri▼): risk of progressive multifocal leukoencephalopathy increases after 2 years of therapy

    mhra · safety · mhra · via natalizumab

  9. Safety communication2014-12-11

    Drug Safety Update: Natalizumab (Tysabri▼): risk of progressive multifocal leukoencephalopathy is increased in patients who have had previous immunosuppressant treatment

    mhra · safety · mhra · via natalizumab

  10. Regulatory approval2014-05-22

    Approval: Entyvio (EMA)

    ema · regulatory · ema · via vedolizumab

  11. New publication2013-08-01
    Vedolizumab as induction and maintenance therapy for ulcerative colitis.

    The New England journal of medicine · 2013 · 1,963 citations · Europe PMC · via vedolizumab

  12. Regulatory approval2006-06-27

    Approval: Tysabri (EMA)

    ema · regulatory · ema · via natalizumab

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.