Protein / target

Programmed cell death protein 1

PDCD1Q15116Homo sapiensSwiss-Prot
UniProt: Q15116Ensembl: ENSG00000188389HGNC: HGNC:8760NCBI Gene: 5133
Clinically validated
Therapeutic maturity
9
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Structure with Ligand

Protein at a glance

Biological role

Transmembrane signaling receptor activity

Primary system

Immune system

Strongest disease association

melanoma

Literature evidence · score 0.63

Therapeutic maturity

Clinically validated target

9 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Structure with Ligand

Clinical development

9 approved · 17 in clinical development

30 linked trials

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

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

Cell membrane
Domains and Gene Ontology detail (14)

Domains & features

Ig-like V-type

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

288 aa · 32 kDa

Biological roles

Reactome v97

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

Immune signallingUniProt · GOSynaptic signallingUniProtKinase signallingUniProtApoptosis & cell deathGO
View supporting evidence

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

Synaptic signalling

  • ·Inhibitory receptor on antigen activated T-cells that plays a critical role in induction…

Kinase signalling

  • ·Inhibitory receptor on antigen activated T-cells that plays a critical role in induction…

Apoptosis & cell death

  • ·apoptotic process
View underlying pathways (3)
Co-inhibition by PD-1
Potential therapeutics for SARS
PD-L1(CD274) glycosylation and translocation to plasma membrane

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.

CD274PDCD1L…PTPN11CD80CD86CTLA4LGALS9PTPN6CD4LAG3PDCD1

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.

Drugs targeting this protein

7

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

pembrolizumab
Narrow target profileApprovedInhibitor

Programmed cell death protein 1 inhibitor

Appears in clinical studies involving melanoma, metastatic melanoma, endometrium neoplasm, head and neck squamous cell carcinoma

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

zimberelimab
Narrow target profilePhase 3Inhibitor

Programmed cell death protein 1 inhibitor

Appears in clinical studies involving non-small cell lung carcinoma, classic Hodgkin lymphoma, gastroesophageal junction adenocarcinoma, gastric adenocarcinoma

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

camrelizumab
Narrow target profilePhase 3Antagonist

Programmed cell death protein 1 antagonist

Appears in clinical studies involving esophageal squamous cell carcinoma, esophageal squamous cell carcinoma, non-small cell squamous lung carcinoma, non-small cell lung carcinoma

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

dostarlimab
Narrow target profileApprovedAntagonist

Programmed cell death protein 1 antagonist

Appears in clinical studies involving endometrial cancer, endometrial neoplasm, neoplasm, peritoneum cancer

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

tislelizumab
Narrow target profileApprovedInhibitor

Programmed cell death protein 1 inhibitor

Appears in clinical studies involving esophageal cancer, Hodgkins lymphoma, non-small cell lung carcinoma, adenocarcinoma

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

spartalizumab
Narrow target profilePhase 3Antagonist

Programmed cell death protein 1 antagonist

Appears in clinical studies involving melanoma, malignant pancreatic neoplasm, invasive ductal breast carcinoma, esophageal squamous cell carcinoma

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

sintilimab
Narrow target profileApprovedAntagonist

Programmed cell death protein 1 antagonist

Appears in clinical studies involving Hodgkins lymphoma, lung adenocarcinoma in situ, non-small cell squamous lung carcinoma, non-small cell lung carcinoma

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

ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

melanoma0.98

Clinical · overall 0.63

non-small cell lung carcinoma0.98

Clinical · overall 0.63

renal cell carcinoma0.97

Clinical · overall 0.61

esophageal squamous cell carcinoma0.95

Clinical · overall 0.61

neoplasm0.94

Clinical · overall 0.60

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

nasopharyngeal carcinoma0.59

Clinical

head and neck squamous cell carcinoma0.59

Literature

Hodgkins lymphoma0.58

Clinical

endometrial cancer0.58

Clinical

squamous cell carcinoma0.56

Clinical

Show all associations
melanoma0.63
non-small cell lung carcinoma0.63
renal cell carcinoma0.61
esophageal squamous cell carcinoma0.61
neoplasm0.60
nasopharyngeal carcinoma0.59
head and neck squamous cell carcinoma0.59
Hodgkins lymphoma0.58
endometrial cancer0.58
squamous cell carcinoma0.56

Open Targets ranks 2,122 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 26 total

CAMRELIZUMABPhase 3

esophageal squamous cell carcinoma · esophageal squamous cell carcinoma · non-small cell squamous lung carcinoma

DOSTARLIMABApproval

endometrial cancer · endometrial neoplasm · neoplasm

FINOTONLIMABPhase 3

head and neck squamous cell carcinoma · non-small cell lung carcinoma · hepatocellular carcinoma

RETIFANLIMABApproval

neuroendocrine carcinoma · Merkel cell skin cancer · squamous cell carcinoma

SINTILIMABApproval

Hodgkins lymphoma · lung adenocarcinoma in situ · non-small cell squamous lung carcinoma

SERPLULIMABApproval

esophageal squamous cell carcinoma · non-small cell lung carcinoma · small cell lung carcinoma

APL-501Phase 2

peripheral T-cell lymphoma, not otherwise specified · alveolar soft part sarcoma · non-Hodgkin lymphoma

TORIPALIMABApproval

melanoma · nasopharyngeal carcinoma · urothelial carcinoma

ZIMBERELIMABPhase 3

non-small cell lung carcinoma · classic Hodgkin lymphoma · gastroesophageal junction adenocarcinoma

BALSTILIMABPhase 3

cervical cancer · metastatic melanoma · metastatic malignant neoplasm

Tractability

SM · Structure with LigandSM · High-Quality LigandAB · Approved DrugAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · LiteraturePR · UniProt UbiquitinationPR · Small Molecule BinderOC · Advanced Clinical

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.

Autologous Activated T-Cells Transduced With A 3rd Generation GD-2 Chimeric Antigen Receptor And iCaspase9 Safety Switch Administered To Patients With Relapsed Or Refractory Neuroblastoma (GRAIN)PHASE1

ACTIVE_NOT_RECRUITING · via pembrolizumab · NCT01822652

A Phase III Randomized Open-Label Study of Single Agent Pembrolizumab vs Physicians' Choice of Single Agent Docetaxel, Paclitaxel, or Irinotecan in Subjects With Advanced/Metastatic Adenocarcinoma and Squamous Cell Carcinoma of the Esophagus That Have Progressed After First-Line Standard Therapy (KEYNOTE-181)PHASE3

COMPLETED · via pembrolizumab · NCT02564263

A Phase 1, First in Human Study of Adenovirally Transduced Autologous Macrophages Engineered to Contain an Anti-HER2 Chimeric Antigen Receptor in Subjects With HER2 Overexpressing Solid TumorsPHASE1

ACTIVE_NOT_RECRUITING · via pembrolizumab · NCT04660929

Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST)NA

ACTIVE_NOT_RECRUITING · via pembrolizumab · NCT02194738

An Open-label, Randomized, Phase 3 Clinical Trial of IO102-IO103 in Combination With Pembrolizumab Versus Pembrolizumab Alone in Patients With Previously Untreated, Unresectable, or Metastatic (Advanced) Melanoma (IO102-IO103-013 / MK3475-D18)PHASE3

ACTIVE_NOT_RECRUITING · via pembrolizumab · NCT05155254

Clinical Efficacy and Safety of Individual Pembrolizumab Administration Based on Pharmacokinetic in Advanced Non-small Cell Lung Cancer: an Open-label, Single Arm, Exploratory Clinical TrialPHASE1

COMPLETED · via pembrolizumab · NCT05226728

Show remaining trials (24)
A Randomized Phase 2 Trial of AM0010 in Combination With Pembrolizumab vs. Pembrolizumab Alone as First-Line (1L) Therapy in Patients With Stage IV / Metastatic Wild Type (WT) Non-Small Cell Lung Cancer and Tumors With High Expression of PD-L1 (> 50%)PHASE2

TERMINATED · via pembrolizumab · NCT03382899

FUTURE Platform Trial - A Phase II Platform Trial of Futibatinib in Combination With (Chemo)Immunotherapy in Colorectal Cancer and Other Solid Tumor EntitiesPHASE2

RECRUITING · via tislelizumab · NCT06722183

Phase 3 Study of Pembrolizumab in Combination With Carboplatin/Taxane (Paclitaxel or Nab-paclitaxel) Followed by Pembrolizumab With or Without Maintenance MK-2870 in the First-line Treatment of Metastatic Squamous Non-small Cell Lung CancerPHASE3

RECRUITING · via pembrolizumab · NCT06422143

ABLE: Phase II, Single Arm, Two-stage Study of Abraxane With Anti-PD1/PDL1 in Patients With Advanced Urothelial CancerPHASE2

COMPLETED · via pembrolizumab · NCT03240016

Synergy of Pembrolizumab Anti-PD-1 Immunotherapy With Chemotherapy for Poorly Chemo-responsive Thyroid and Salivary Gland Tumors. The iPRIME Study.PHASE2

ACTIVE_NOT_RECRUITING · via pembrolizumab · NCT03360890

A Phase Ib/II Randomised Open Label Study of BGB324 in Combination With Pembrolizumab or Dabrafenib/Trametinib Compared to Pembrolizumab or Dabrafenib/Trametinib Alone, in Patients With Advanced Non-resectable (Stage IIIc) or Metastatic (Stage IV) MelanomaPHASE1/PHASE2

COMPLETED · via pembrolizumab · NCT02872259

A Randomized, Placebo-Controlled, Double-Blind Phase 3 Study to Evaluate the Efficacy and Safety of Tislelizumab (BGB-A317) in Combination With Chemotherapy as First-Line Treatment in Patients With Unresectable, Locally Advanced Recurrent or Metastatic Esophageal Squamous Cell CarcinomaPHASE3

COMPLETED · via tislelizumab · NCT03783442

An Open-label, Multicenter, Phase 1/2 Study of Radium-223 Dichloride in Combination With Pembrolizumab in Participants With Stage IV Non-small Cell Lung CancerPHASE1

TERMINATED · via pembrolizumab · NCT03996473

A Phase I Study of MK-3475 Alone in Subjects With Advanced Solid Tumors and in Combination With Platinum-Doublet Chemotherapy or Immunotherapy in Subjects With Advanced Non-Small Cell Lung Cancer/Extensive-Disease Small Cell Lung Cancer.PHASE1

COMPLETED · via pembrolizumab · NCT01840579

A Randomized Open Label Phase II Study of Immune Checkpoint Inhibitor Combinations With Axitinib in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic Renal Cell CarcinomaPHASE2

ACTIVE_NOT_RECRUITING · via pembrolizumab · NCT05805501

A Biomarker-Directed, Multi-Centre Phase II/III Study of CTDNA Response Adaptive Immuno-Chemotherapy in Lung CancerPHASE2/PHASE3

RECRUITING · via pembrolizumab · NCT04093167

A Phase 2/3, Randomized, Double-Blind, Controlled Study of Zanzalintinib (XL092) in Combination With Pembrolizumab vs Pembrolizumab in First-Line Treatment of Subjects With PD-L1 Positive Recurrent or Metastatic Head and Neck Squamous Cell CarcinomaPHASE2/PHASE3

ACTIVE_NOT_RECRUITING · via pembrolizumab · NCT06082167

Eight Vs Four Cycles of Preoperative Neoadjuvant Sintilimab in Mismatch-repair Deficient/microsatellite Instability-high, Locally Advanced Colorectal Cancer(OPEN): a Multi-center, Open-label, Prospective Randomized Controlled TrialPHASE2

RECRUITING · via sintilimab · NCT06698757

SUNRAY-01, A Global Pivotal Study in Participants With KRAS G12C-Mutant, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Comparing First-Line Treatment of LY3537982 and Pembrolizumab vs Placebo and Pembrolizumab in Those With PD-L1 Expression ≥50% or LY3537982 and Pembrolizumab, Pemetrexed, Platinum vs Placebo and Pembrolizumab, Pemetrexed, Platinum Regardless of PD-L1 ExpressionPHASE3

RECRUITING · via pembrolizumab · NCT06119581

A Phase II Study of Cryoablation Combined with Anti-PD-1 Antibody （SHR-1210） in Patients with Advanced Intrahepatic CholangiocarcinomaPHASE2

RECRUITING · via camrelizumab · NCT04299581

A Clinical Study of Sintilimab as Adjuvant Therapy in Node-positive Esophageal Squamous Cell Carcinoma After Radical Surgery Without Neoadjuvant TherapyPHASE2

RECRUITING · via sintilimab · NCT06190639

A Phase 1b/2, Randomized, Open-Label Study Investigating the Efficacy and Safety of LBL-007 Plus Tislelizumab in Combination With Bevacizumab Plus Fluoropyrimidine Versus Bevacizumab Plus Fluoropyrimidine as Maintenance Therapy in Patients With Unresectable or Metastatic Microsatellite Stable/Mismatch Repair Proficient Colorectal CancerPHASE1/PHASE2

ACTIVE_NOT_RECRUITING · via tislelizumab · NCT05609370

A Phase 2, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Setanaxib, When Administered With Pembrolizumab, in Patients With Recurrent or Metastatic SCCHNPHASE2

COMPLETED · via pembrolizumab · NCT05323656

Sintilimab in the Treatment of Advanced and Refractory Pediatric Malignant Tumors-A Phase I StudyPHASE1

UNKNOWN · via sintilimab · NCT04400851

Camrelizumab Combined With Apatinib in the Treatment of Patients With Advanced Gastric Cancer and Colorectal Cancer：One-arm Exploratory Clinical TrialPHASE1/PHASE2

UNKNOWN · via camrelizumab · NCT04067986

Phase Ib/II Non-randomized Non-comparative Two-cohort Study of Niraparib and Dostarlimab Plus (Chemo)RadIotherapy in Locally-Advanced Head and Neck Squamous Cell CarcinomaPHASE1/PHASE2

ACTIVE_NOT_RECRUITING · via dostarlimab · NCT05784012

A Phase 2, Two-stage, Study of Mirvetuximab Soravtansine (IMGN853) in Combination With Pembrolizumab in Patients With Microsatellite Stable (MSS) Recurrent or Persistent Endometrial Cancer (EC)PHASE2

ACTIVE_NOT_RECRUITING · via pembrolizumab · NCT03835819

Stop and go Strategy as First-line Treatment in Patients With Objective Response After Systematic Chemotherapy for Widely de Novo Metastatic Nasopharyngeal Carcinoma: A Phase II TrialPHASE2

NOT_YET_RECRUITING · via tislelizumab · NCT06331845

A Phase 1 Study to Evaluate the Safety and Tolerability of AB154 Monotherapy and Combination Therapy in Participants With Advanced MalignanciesPHASE1

COMPLETED · via zimberelimab · NCT03628677

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

melanomaWell supported
0.78
agreement 0.62–0.93
Clinical83%Literature17%

Open Targets aggregate 0.63 · 2 independent evidence families

non-small cell lung carcinomaWell supported
0.78
agreement 0.62–0.93
Clinical83%Literature17%

Open Targets aggregate 0.63 · 2 independent evidence families

renal cell carcinomaWell supported
0.76
agreement 0.61–0.92
Clinical85%Literature15%

Open Targets aggregate 0.61 · 2 independent evidence families

esophageal squamous cell carcinomaWell supported
0.75
agreement 0.60–0.91
Clinical84%Literature16%

Open Targets aggregate 0.61 · 2 independent evidence families

neoplasmWell supported
0.75
agreement 0.60–0.91
Clinical83%Literature18%

Open Targets aggregate 0.60 · 2 independent evidence families

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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

60

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

  1. Trial results posted2026-07-20

    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.

    Results posted · ClinicalTrials.gov · via pembrolizumab

  2. Trial status changed2026-07-20

    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.

    Status changed to Completed · ClinicalTrials.gov · via pembrolizumab

  3. Trial status changed2026-07-16

    A Pilot Study of Pembrolizumab and Lenvatinib Combination Therapy in Patients With Previously Treated Advanced Gastroesophageal Adenocarcinoma

    Status changed to Active, not recruiting · ClinicalTrials.gov · via pembrolizumab

  4. Indication expanded2026-07-10

    Indication expansion: PEMBROLIZUMAB AND BERAHYALURONIDASE ALFA-PMPH (BLA761467)

    fda · regulatory · fda · via pembrolizumab

  5. Indication expanded2026-07-10

    Indication expansion: PEMBROLIZUMAB (BLA125514)

    fda · regulatory · fda · via pembrolizumab

  6. Indication expanded2026-06-24

    Indication expansion: PEMBROLIZUMAB AND BERAHYALURONIDASE ALFA-PMPH (BLA761467)

    fda · regulatory · fda · via pembrolizumab

  7. Indication expanded2026-06-24

    Indication expansion: PEMBROLIZUMAB (BLA125514)

    fda · regulatory · fda · via pembrolizumab

  8. Regulatory action2026-06-15
    Merck's Welireg-Keytruda pairing sticks the landing in adjuvant kidney cancer treatment with new FDA nod

    Fierce Pharma · news · via pembrolizumab

  9. Indication expanded2026-06-12

    Indication expansion: PEMBROLIZUMAB AND BERAHYALURONIDASE ALFA-PMPH (BLA761467)

    fda · regulatory · fda · via pembrolizumab

  10. Indication expanded2026-06-12

    Indication expansion: PEMBROLIZUMAB (BLA125514)

    fda · regulatory · fda · via pembrolizumab

  11. Label change2026-05-12

    Label change: PEMBROLIZUMAB AND BERAHYALURONIDASE ALFA-PMPH (BLA761467)

    fda · regulatory · fda · via pembrolizumab

  12. Label change2026-05-12

    Label change: PEMBROLIZUMAB (BLA125514)

    fda · regulatory · fda · via pembrolizumab

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.