Protein / target

Proteinase-activated receptor 1

Encoded byF2RP25116Homo sapiensSwiss-Prot

UniProt: P25116 Ensembl: ENSG00000181104 HGNC: HGNC:3537 NCBI Gene: 2149

Clinically validated

Therapeutic maturity

Approved medicines

Open Targets target-level

Clinical trials

Small-molecule tractable

Druggability

Approved Drug

Protein at a glance

Biological role

Thrombin-activated receptor

Strongest disease association

Pre-Eclampsia

Via encoding gene F2R · Genetic evidence · score 0.42

Therapeutic position

Established drug target

Small molecules

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

High affinity receptor that binds the activated thrombin, leading to calcium release from intracellular stores.

View complete UniProt function annotation

High affinity receptor that binds the activated thrombin, leading to calcium release from intracellular stores (PubMed:1672265, PubMed:8136362). The thrombin-activated receptor signaling pathway is mediated through PTX-insensitive G proteins, activation of phospholipase C resulting in the production of 1D-myo-inositol 1,4,5-trisphosphate (InsP3) which binds to InsP3 receptors causing calcium release from the stores (By similarity). In astrocytes, the calcium released into the cytosol allows the Ca(2+)-dependent release of L-glutamate into the synaptic cleft through BEST1, that targets the neuronal postsynaptic GRIN2A/NMDAR receptor resulting in the synaptic plasticity regulation (By similarity). May play a role in platelets activation and in vascular development (PubMed:10079109). Mediates up-regulation of pro-inflammatory cytokines, such as MCP-1/CCL2 and IL6, triggered by coagulation factor Xa (F10) in cardiac fibroblasts and umbilical vein endothelial cells (PubMed:30568593, PubMed:34831181)

Subcellular location

Cell membrane

Domains and Gene Ontology detail (56)

Gene Ontology

Ccaveola
Ccell surface
Cearly endosome
Cextracellular region
CGolgi apparatus
Clate endosome
Cneuromuscular junction
Cplasma membrane
Cplatelet dense tubular network
Cpostsynaptic membrane
FG protein-coupled receptor activity
FG-protein alpha-subunit binding

425 aa · 47 kDa

Biological roles

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

Synaptic signallingUniProt · GOCell proliferation & survivalGOCell migrationGOImmune signallingUniProt · GOHaemostasisUniProt · GOG protein-coupled signallingGO

View supporting evidence

Synaptic signalling

·High affinity receptor that binds the activated thrombin, leading to calcium release fro…
·postsynaptic membrane
·trans-synaptic signaling by endocannabinoid, modulating synaptic transmission

Cell proliferation & survival

·negative regulation of cell population proliferation
·positive regulation of cell population proliferation

Cell migration

·positive regulation of cell migration

Immune signalling

·High affinity receptor that binds the activated thrombin, leading to calcium release fro…
·connective tissue replacement involved in inflammatory response wound healing
·inflammatory response
·positive regulation of interleukin-6 production

Haemostasis

·High affinity receptor that binds the activated thrombin, leading to calcium release fro…
·platelet dense tubular network
·platelet activation
·platelet dense granule organization

G protein-coupled signalling

·G protein-coupled receptor activity
·G protein-coupled receptor signaling pathway
·phospholipase C-activating G protein-coupled receptor signaling pathway

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

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.

PZ-128

Narrow target profilePhase 2Inhibitor

Proteinase-activated receptor 1 inhibitor

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 F2R

Gene-level evidence surfaced through the gene F2Rthat 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.

Myocardial Infarction

0.68Moderately supported

Clinical evidence dominant · Open Targets 0.55

Peripheral Arterial Disease

0.58Moderately supported

Clinical evidence dominant · Open Targets 0.47

Stroke

0.47Limited support

Clinical evidence dominant · Open Targets 0.38

Pre-Eclampsia

0.46Limited support

Genetic evidence dominant · Open Targets 0.27

Neurodegenerative Diseases

0.34Preliminary

Pathway evidence dominant · Open Targets 0.49 · no direct causal or clinical evidence

View evidence synthesis (5)

Myocardial InfarctionModerately supported

0.68

agreement 0.52–0.83

Clinical96%Literature4%

Open Targets aggregate 0.55 · 2 independent evidence families

Peripheral Arterial DiseaseModerately supported

0.58

agreement 0.42–0.73

Clinical97%Literature3%

Open Targets aggregate 0.47 · 2 independent evidence families

StrokeLimited support

0.47

agreement 0.32–0.63

Clinical94%Literature6%

Open Targets aggregate 0.38 · 2 independent evidence families

Pre-EclampsiaLimited support

0.46

agreement 0.32–0.59

Genetic88%Literature13%

Open Targets aggregate 0.27 · 2 independent evidence families

Neurodegenerative DiseasesPreliminary

0.34

agreement 0.16–0.52

Pathway93%Literature7%

Open Targets aggregate 0.49 · 2 independent evidence families · no direct causal or clinical evidence

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

Myocardial Infarction0.55

Neurodegenerative Diseases0.49

Peripheral Arterial Disease0.47

Stroke0.38

Pre-Eclampsia0.27

von Willebrand disease 10.19

Dermatitis0.16

Neoplasms0.12

Coronary Artery Disease0.12

Drug development

4 compounds recorded · 2 approved · 2 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph: these count different sets and are not a subset relation.

View all recorded compounds (4)

PZ-128Phase 2

ATOPAXARPhase 2

VORAPAXAR SULFATEApproval

VORAPAXARApproval

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

Approved Drug and Structure with Ligand support this modality.

Antibodies — Emerging

Feasibility evidence (go cc high conf and uniprot loc med conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination and small molecule binder) — no clinical-stage drug of this modality recorded.

Other modalities — Strong

Advanced Clinical support this modality.

View underlying tractability evidence (10)

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Small Molecule BinderOC · Advanced Clinical

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.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety of PZ-128 in Subjects Undergoing Non-Emergent Percutaneous Coronary Intervention- Thrombin Receptor Inhibitory Pepducin in PCI (TRIP-PCI)PHASE2

COMPLETED · via PZ-128 · NCT02561000

Demonstration of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Antiplatelet Effect of PZ-128 in Subjects With Multiple Coronary Artery Disease Risk FactorsPHASE1

COMPLETED · via PZ-128 · NCT01806077

ClinicalTrials.gov via the drug-target graph.