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Protein / target

Cytotoxic T-lymphocyte protein 4

Encoded byCTLA4P16410Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
2
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Structure with Ligand

Protein at a glance

Biological role

Receptor decoy

Strongest disease association

Hypothyroidism

Via encoding gene CTLA4 · Genetic evidence · score 0.96

Therapeutic position

Established drug target

Antibodies

Research activity

Actively researched

56 papers · latest 2026

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

Inhibitory receptor acting as a major negative regulator of T-cell responses.

View complete UniProt function annotation

Inhibitory receptor acting as a major negative regulator of T-cell responses (PubMed:11279501, PubMed:11279502, PubMed:16551244, PubMed:1714933, PubMed:18641304, PubMed:28484017). Acts as a decoy receptor: the affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of their cognate stimulatory coreceptor CD28 (PubMed:11279501, PubMed:11279502, PubMed:16551244, PubMed:1714933, PubMed:28484017)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (19)

Domains & features

Ig-like V-type

Gene Ontology

  • Cclathrin-coated endocytic vesicle
  • Cexternal side of plasma membrane
  • CGolgi apparatus
  • Cperinuclear region of cytoplasm
  • Cplasma membrane
  • Cprotein complex involved in cell adhesion
  • Freceptor decoy activity
  • Padaptive immune response
  • PB cell receptor signaling pathway
  • PDNA damage response
  • Pimmune response
  • Pnegative regulation of B cell proliferation

223 aa · 25 kDa · 5 isoforms

Biological roles

Reactome v97

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

Immune signallingGO
View supporting evidence

Immune signalling

  • ·adaptive immune response
  • ·B cell receptor signaling pathway
  • ·immune response
  • ·negative regulation of B cell 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.

CD86LOC102…CD80CD274ICOSPDCD1L…PDCD1ICOSLGLGALS9CD28CTLA4

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

2 medicines · 6 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, Non-Small-Cell Lung2 medicines
Carcinoma, Hepatocellular1 medicine
Carcinoma, Renal Cell1 medicine
Colorectal Neoplasms1 medicine
Melanoma1 medicine
Broader indication categories (1)
Neoplasms2 medicines

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.

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.

tremelimumab
Narrow target profileApprovedInhibitor

Cytotoxic T-lymphocyte protein 4 inhibitor

Indicated for Carcinoma, Hepatocellular, Carcinoma, Non-Small-Cell Lung, Neoplasms

Direct interaction with this protein · Only this protein recorded as a target

ipilimumab
Narrow target profileApprovedInhibitor

Cytotoxic T-lymphocyte protein 4 inhibitor

Indicated for Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell, Colorectal Neoplasms, Melanoma

Direct interaction with this protein · Only this protein recorded as a target

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 CTLA4

Gene-level evidence surfaced through the gene CTLA4that 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.

Hypothyroidism
0.96Well supported

Genetic evidence dominant · Open Targets 0.59

Arthritis, Rheumatoid
0.95Well supported

Genetic evidence dominant · Open Targets 0.60

Graves' Disease
0.94Well supported

Genetic evidence dominant · Open Targets 0.58

Diabetes Mellitus, Type 1
0.93Well supported

Genetic evidence dominant · Open Targets 0.59

autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
0.89Well supported

Genetic evidence dominant · Open Targets 0.80

View evidence synthesis (5)
HypothyroidismWell supported
0.96
agreement 0.821.00
Genetic96%Literature4%

Open Targets aggregate 0.59 · 2 independent evidence families

Arthritis, RheumatoidWell supported
0.95
agreement 0.811.00
Genetic87%Literature13%

Open Targets aggregate 0.60 · 2 independent evidence families

Graves' DiseaseWell supported
0.94
agreement 0.801.00
Genetic94%Literature6%

Open Targets aggregate 0.58 · 2 independent evidence families

Diabetes Mellitus, Type 1Well supported
0.93
agreement 0.791.00
Genetic87%Literature13%

Open Targets aggregate 0.59 · 2 independent evidence families

autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiencyWell supported
0.89
agreement 0.771.00
Genetic81%Animal model17%Literature2%Genetic literaturedup

Open Targets aggregate 0.80 · 3 independent evidence families · 1 not counted as duplicate

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
autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency0.80
Hashimoto's Disease0.67
Lupus Erythematosus, Systemic0.62
Melanoma0.61
Carcinoma, Non-Small-Cell Lung0.61
Carcinoma, Hepatocellular0.61
Arthritis, Rheumatoid0.60
Hypothyroidism0.59
Diabetes Mellitus, Type 10.59
Graves' Disease0.58

Drug development

6 compounds recorded · 2 approved · 4 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 (6)
QUAVONLIMABPhase 3
ZALIFRELIMABPhase 2
CADONILIMABPhase 3
ERFONRILIMABPhase 3
IPILIMUMABApproval
TREMELIMUMABApproval

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 moleculesEmerging

Feasibility evidence (structure with ligand) — no clinical-stage drug of this modality recorded.

AntibodiesStrong

Approved Drug and UniProt loc high conf support this modality.

View underlying tractability evidence (5)
SM · Structure with LigandAB · Approved DrugAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMM

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

a hypersensitivity reactionClinPGxgingival overgrowthClinPGxlater onset of bortezomib-induced peripheral neuropathyClinPGxearlier onset of bortezomib-induced peripheral neuropathyClinPGxparadoxical psoriasiform reactionsClinPGx

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 ipilimumab · NCT05647265

ACTIVE_NOT_RECRUITING · via ipilimumab · NCT05289193

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. Label change2026-06-12

    Label change: IPILIMUMAB (BLA125377)

    fda · regulatory · fda · via ipilimumab

  2. Indication expanded2025-05-23

    Indication expansion: IPILIMUMAB (BLA125377)

    fda · regulatory · fda · via ipilimumab

  3. Indication expanded2025-04-11

    Indication expansion: IPILIMUMAB (BLA125377)

    fda · regulatory · fda · via ipilimumab

  4. Indication expanded2025-04-08

    Indication expansion: IPILIMUMAB (BLA125377)

    fda · regulatory · fda · via ipilimumab

  5. Indication expanded2025-01-28

    Indication expansion: IPILIMUMAB (BLA125377)

    fda · regulatory · fda · via ipilimumab

  6. New publication2024-08-06
    Randomized, open-label, phase 2 study of nivolumab plus ipilimumab or nivolumab monotherapy in patients with advanced or metastatic solid tumors of high tumor mutational burden.

    Journal for immunotherapy of cancer · 2024 · 30 citations · Europe PMC · via ipilimumab

  7. New publication2024-08-01
    Plasma versus Tissue Tumor Mutational Burden as Biomarkers of Durvalumab plus Tremelimumab Response in Patients with Metastatic Colorectal Cancer in the CO.26 Trial.

    Clinical cancer research : an official journal of the American Association for Cancer Research · 2024 · 15 citations · Europe PMC · via tremelimumab

  8. New publication2024-07-02
    Final Results From a Phase I Trial and Expansion Cohorts of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced/Metastatic Genitourinary Tumors.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024 · 18 citations · Europe PMC · via ipilimumab

  9. New publication2024-06-01
    Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair-Deficient Colon Cancer.

    The New England journal of medicine · 2024 · 213 citations · Europe PMC · via ipilimumab

  10. New publication2024-01-02
    Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial.

    Nature communications · 2024 · 61 citations · Europe PMC · via ipilimumab

  11. Regulatory approval2023-02-20

    Approval: Imjudo (EMA)

    ema · regulatory · ema · via tremelimumab

  12. Safety communication2019-01-09

    Drug Safety Update: Ipilimumab (Yervoy): reports of cytomegalovirus (CMV) gastrointestinal infection or reactivation

    mhra · safety · mhra · via ipilimumab

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

56 papers · to 2026

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

Most cited

Recent

Immune checkpoint inhibition perturbs neuro-immune homeostasis and impairs cognitive function.

Ifejeokwu OV · Journal of experimental & clinical cancer research : CR · 2025

Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer.

Robles-Oteíza C · The Journal of experimental medicine · 2025

Soluble CTLA-4 attenuates T cell activation and modulates anti-tumor immunity.

Kennedy PT · Molecular therapy : the journal of the American Society of Gene Therapy · 2024

Europe PMC papers linked directly to this protein.