Protein / target
Programmed cell death protein 1
Protein at a glance
Biological role
Transmembrane signaling receptor
Strongest disease association
Melanoma
Therapeutic position
Established drug target
Research activity
Extensively researched
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self.
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Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:31754127, PubMed:32184441, PubMed:37208329). Delivers inhibitory signals upon binding to ligands CD274/PDCD1L1 and CD273/PDCD1LG2 (PubMed:21276005, PubMed:26602187). Following T-cell receptor (TCR) engagement, PDCD1 associates with TCR-CD3 in the immunological synapse and directly inhibits T-cell activation (PubMed:32184441). Suppresses T-cell activation through the recruitment of PTPN11/SHP-2: following ligand-binding, PDCD1 is phosphorylated within the ITSM motif, leading to the recruitment of the protein tyrosine phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta (PubMed:32184441)
Subcellular location
Domains and Gene Ontology detail (14)Hide
Domains & features
Gene Ontology
- Cexternal side of plasma membrane
- Cplasma membrane
- Fsignaling receptor activity
- Ftransmembrane signaling receptor activity
- Padaptive immune response
- Papoptotic process
- Phumoral immune response
- Pnegative regulation of immune response
- Pnegative regulation of inflammatory response
- Pnegative regulation of T cell activation
- Pnegative regulation of T cell mediated immune response to tumor cell
- Pnegative regulation of T cell receptor signaling pathway
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Immune signalling
- ·Inhibitory receptor on antigen activated T-cells that plays a critical role in induction…
- ·adaptive immune response
- ·humoral immune response
- ·negative regulation of immune response
View underlying pathways (3)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
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.
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
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.
Broader indication categories (1)Hide
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.
9 medicines meet Open Targets' target-level approved-medicine definition; the 5 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
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.
Programmed cell death protein 1 inhibitor
Indicated for Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell, Carcinoma, Squamous Cell, Carcinoma, Transitional Cell
Programmed cell death protein 1 inhibitor
Programmed cell death protein 1 antagonist
Programmed cell death protein 1 antagonist
Indicated for Endometrial Neoplasms, Neoplasms
Programmed cell death protein 1 inhibitor
Indicated for Adenocarcinoma, Carcinoma, Non-Small-Cell Lung, Esophageal Neoplasms, Esophageal Squamous Cell Carcinoma
Programmed cell death protein 1 antagonist
View all 11 targeting drugsHide
Programmed cell death protein 1 antagonist
Programmed cell death protein 1 inhibitor
Indicated for Carcinoma, Squamous Cell, Lung Neoplasms, Neoplasms
Programmed cell death protein 1 antagonist
Programmed cell death protein 1 antagonist
Indicated for Nasopharyngeal Carcinoma, Neoplasms
Programmed cell death protein 1 inhibitor
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
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 PDCD1
Gene-level evidence surfaced through the gene PDCD1 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.
View evidence synthesis (5)Hide
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.
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Drug development
26 compounds recorded · 9 approved · 17 in clinical development
View all recorded compounds (10)Hide
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 — Emerging
Antibodies — Strong
Protein degraders — Emerging
Other modalities — Strong
View underlying tractability evidence (10)Hide
Raw Open Targets tractability assessment buckets, by modality.
Clinical trials
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)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 3 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.
- Trial status changed
A Phase 3 Open-Label, Randomized Study of PDS0101 and Pembrolizumab vs Pembrolizumab Alone in First-Line Treatment of Unresectable Recurrent and/or Metastatic HPV16+ Head and Neck Squamous Cell Carcinoma
- Indication expanded
Indication expansion: TISLELIZUMAB-JSGR (BLA761232)
- Product recall
Recall (Class II): CEMIPLIMAB-RWLC
- Trial results posted
Cemiplimab in High-risk or Locally Advanced Luminal and Triple Negative Breast Cancer (CemiHALT )
- Trial results posted
A Phase 3, Randomized Study to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) + Lenvatinib (E7080/MK-7902) + Chemotherapy Compared With Standard of Care as First-line Intervention in Participants With Metastatic Esophageal Carcinoma.
- Trial status changed
A Phase 3, Randomized Study to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) + Lenvatinib (E7080/MK-7902) + Chemotherapy Compared With Standard of Care as First-line Intervention in Participants With Metastatic Esophageal Carcinoma.
- Indication expanded
Indication expansion: PEMBROLIZUMAB (BLA125514)
- Indication expanded
Indication expansion: PEMBROLIZUMAB AND BERAHYALURONIDASE ALFA-PMPH (BLA761467)
- Indication expanded
Indication expansion: PEMBROLIZUMAB (BLA125514)
- New publicationFecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial.
- New publicationSacituzumab Govitecan plus Pembrolizumab for Advanced Triple-Negative Breast Cancer.
- New publicationPhase I and II Clinical Studies of the STING Agonist Ulevostinag with and without Pembrolizumab in Participants with Advanced or Metastatic Solid Tumors or Lymphomas.
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
Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.
Most cited
Recent
Europe PMC papers linked directly to this protein.