ITGA4 integrin subunit alpha 4
ENSG00000115232 · protein coding · Open Targets profile
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). {ECO:0000269|PubMed:18635536, ECO:0000269|PubMed:19064666, ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:25398877, ECO:0000269|PubMed:35802072}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Advanced Clinical, Structure with Ligand, High-Quality Ligand, Druggable Family
- Antibody
- Approved Drug, GO CC high conf, UniProt SigP or TMHMM, Human Protein Atlas loc
- PROTAC
- Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.4715000092983246 (upper bound 0.581529974937439). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 92 registry trials, updated in the last three years, of the most advanced drugs against ITGA4 (natalizumab, vedolizumab, firategrast, abrilumab, UCB-1184197), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Vipul JairathAlimentiv Inc. · 2 of 2 trials Phase 2+
- Eveline SchurinkAlvotech Swiss AG · 1 of 2 trials Phase 2+
- Yinghong WangM.D. Anderson Cancer Center · 1 of 2 trials Phase 2+
- Agnes RethyPolpharma Biologics S.A. · 1 of 1 trials Phase 2+
- Anthony BuissonUniversity Hospital, Clermont-Ferrand · 1 of 1 trials Phase 2+
- Bianca Weinstock-GuttmanSUNY Buffalo · 1 of 1 trials Phase 2+
- Daniel OntanedaThe Cleveland Clinic · 1 of 1 trials Phase 2+
- Francesca BagnatoVanderbilt University Medical Center · 1 of 1 trials Phase 2+
- Freddy CalderaUW School of Medicine and Public Health · 1 of 1 trials Phase 2+
- G.R.A.M. D'HaensAmsterdam UMC · 1 of 1 trials Phase 2+
- George E. GeorgesNorthwestern University · 1 of 1 trials Phase 2+
- Guillaume BOUGUENRennes University Hospital · 1 of 1 trials Phase 2+
- Isabelle T SeemannTherakos LLC · 1 of 1 trials Phase 2+
- Javier P GisbertFundación de Investigación Biomédica - Hospital Universitario de La Princesa · 1 of 1 trials Phase 2+
- Jeffrey A. CohenMellen Center for MS Treatment and Research, Cleveland Clinic · 1 of 1 trials Phase 2+
Registry trials of natalizumab, vedolizumab, firategrast, abrilumab, UCB-1184197 updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 64 of 89 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 3 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
46 trials of drugs against ITGA4 were stopped early; 6 give no reason
Terminated, withdrawn and suspended interventional trials of natalizumab, vedolizumab, firategrast, abrilumab, UCB-1184197, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 46.
- terminated · 2026-05-06 · Mats Remberger · matched by the registry's drug synonyms“Too slow recruitment”
- terminated · 2026-03-16 · University Hospital, Strasbourg, France · matched by the registry's drug synonymsNo reason given
- terminated · 2025-12-26 · Alvotech Swiss AG · Vedolizumab“The study has been terminated based on Sponsor decision. This decision is not related to any safety concerns associated with the investigational products. It is related to the fact that study will be not required for product dossier submission.”
- withdrawn · 2025-12-26 · Therakos LLC · Vedolizumab“Study Withdrawn by Sponsor prior to Enrollment.”
- terminated · 2025-11-25 · Biogen · Natalizumab“Due to sponsor decision, not for efficacy or safety reasons.”
- withdrawn · 2025-01-15 · Case Comprehensive Cancer Center · Natalizumab“No accruals”
- terminated · 2024-06-21 · Biogen · Natalizumab“Sponsor's decision”
- withdrawn · 2024-06-03 · Biogen · matched by the registry's drug synonyms“Sponsor decision to withdraw study at this time.”
- terminated · 2024-06-03 · Biogen · natalizumab“Sponsor's decision.”
- terminated · 2024-04-18 · Vanderbilt University Medical Center · Natalizumab 300 MG in 15 ML Injection“Sponsor declined further support”
- terminated · 2024-04-10 · Centre Hospitalier Universitaire de Saint Etienne · matched by the registry's drug synonyms“low of inclusions”
- terminated · 2024-03-05 · Millennium Pharmaceuticals, Inc. · vedolizumab“Business decision: Protocol efficacy futility met”
- terminated · 2023-11-18 · Takeda · Vedolizumab“Early Completed - Alternative Source of Drug Available”
- terminated · 2023-06-15 · Centre Hospitalier Universitaire de Saint Etienne · Vedolizumab“low inclusion rates”
- terminated · 2023-05-23 · Centre Hospitalier Universitaire de Saint Etienne · matched by the registry's drug synonyms“The study was stopped due to lack of inclusions”
- terminated · 2023-02-17 · Nantes University Hospital · VEDOLIZUMAB“the CELLVIZIO device required to analyse biopsy is available until september 2020”
- withdrawn · 2022-11-25 · Icahn School of Medicine at Mount Sinai · matched by the registry's drug synonyms“Lack on enrollment”
- withdrawn · 2021-05-06 · Eli Lilly and Company · Vedolizumab IV“The trial was terminated secondary to a business decision, the original scientific question rendered moot by the external scientific community.”
- withdrawn · 2020-10-27 · Takeda · Vedolizumab“No enrollment”
- terminated · 2020-09-03 · Medical College of Wisconsin · Vedolizumab“insufficient enrollment”
- withdrawn · 2020-05-14 · Marc Schwartz · Vedolizumab“Limited time for enrollment of required number of subjects”
- terminated · 2019-09-27 · Biogen · matched by the registry's drug synonyms“Study terminated in line with Biogen decision to withdraw Zinbryta from the market and not to pursue further studies of daclizumab in MS.”
- terminated · 2019-08-29 · ANRS, Emerging Infectious Diseases · GTU-MultiHIV B-clade vaccine + MVA HIV-B HIV vaccine+ Vedolizumab, Vedolizumab 300 MG [Entyvio]“Due to the bankruptcy of FITBiotech, the provider of the GTU DNA vaccine.”
- withdrawn · 2019-07-08 · University of Pennsylvania · Vedolizumab“No patient accrual”
- terminated · 2019-05-24 · Millennium Pharmaceuticals, Inc. · Vedolizumab“Lack of efficacy of the drug; no safety concern”
Paediatric incentives and obligations for ITGA4's drugs
For natalizumab, vedolizumab, firategrast, abrilumab, UCB-1184197: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · ITGA4 is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMEA-000645-PIP01-09-M09 (vedolizumab, Treatment of Crohn's disease;Treatment of ulcerative colitis): PM: decision on the application for modification of an agreed PIP, 18 Jul 2024; EMEA-000645-PIP04-20-M02 (vedolizumab, Treatment of pouchitis): PM: decision on the application for modification of an agreed PIP, 7 Sept 2023; EMEA-000645-PIP03-18 (vedolizumab, Prevention of acute graft-versus-host disease): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 14 Aug 2019; EMEA-001095-PIP03-19 (natalizumab, Treatment of multiple sclerosis): W: decision granting a waiver in all age groups for all conditions or indications, 18 Mar 2020; +2 moreRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: no · No EU orphan designation names natalizumab, vedolizumab, firategrast, abrilumab, ucb-1184197Rule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Entyvio: authorised since 22 May 2014; Tyruko: authorised since 22 Sept 2023; Tysabri: authorised since 27 Jun 2006; Natalizumab Elan Pharma: refusedRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of natalizumab, vedolizumab, firategrast, abrilumab, ucb-1184197Rule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 21 interventional studies of natalizumab, vedolizumab, firategrast, abrilumab, ucb-1184197 include patients under 18; 9 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-12
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 5 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.