Protein / target

Prothrombin

F2P00734Homo sapiensSwiss-Prot
UniProt: P00734Ensembl: ENSG00000180210HGNC: HGNC:3535NCBI Gene: 2147
Clinically validated
Therapeutic maturity
11
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Serine-type endopeptidase activity

Primary system

Immune system

Strongest disease association

congenital prothrombin deficiency

Genetic evidence · score 0.94

Therapeutic maturity

Clinically validated target

11 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

11 approved · 3 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

Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing. Activates coagulation factor XI (F11); activation is promoted by the contact with negatively charged surfaces (PubMed:2019570, PubMed:21976677). Triggers the production of pro-inflammatory cytokines, such as MCP-1/CCL2 and IL8/CXCL8, in endothelial cells (PubMed:30568593, PubMed:9780208)

Subcellular location

Secreted, extracellular space
Domains and Gene Ontology detail (46)

Domains & features

GlaKringle 1Kringle 2Peptidase S1

Gene Ontology

  • Cblood microparticle
  • Cendoplasmic reticulum lumen
  • Cextracellular exosome
  • Cextracellular matrix
  • Cextracellular region
  • Cextracellular space
  • CGolgi lumen
  • Cplasma membrane
  • Fcalcium ion binding
  • Fgrowth factor activity
  • Fheparin binding
  • Flipopolysaccharide binding

622 aa · 70 kDa

Biological roles

Reactome v97

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

HaemostasisUniProt · GO · ReactomeImmune signallingUniProt · GOProteolysisGOG protein-coupled signallingGOCell adhesionGOMetabolic enzyme activityGO
View supporting evidence

Haemostasis

  • ·Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activ…
  • ·blood coagulation
  • ·fibrinolysis
  • ·negative regulation of blood coagulation

Immune signalling

  • ·Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activ…
  • ·antimicrobial humoral immune response mediated by antimicrobial peptide
  • ·cytolysis by host of symbiont cells
  • ·negative regulation of cytokine production involved in inflammatory response

Proteolysis

  • ·serine-type endopeptidase activity
  • ·negative regulation of proteolysis
  • ·proteolysis

G protein-coupled signalling

  • ·positive regulation of phospholipase C-activating G protein-coupled receptor signaling p…

Cell adhesion

  • ·extracellular matrix

Metabolic enzyme activity

  • ·positive regulation of reactive oxygen species metabolic process
View underlying pathways (17)
Gamma-carboxylation of protein precursors
Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus
Removal of aminoterminal propeptides from gamma-carboxylated proteins
Cell surface interactions at the vascular wall
Peptide ligand-binding receptors
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
G alpha (q) signalling events
Thrombin signalling through proteinase activated receptors (PARs)
Platelet Aggregation (Plug Formation)
Defective factor XII causes hereditary angioedema
Defective F8 cleavage by thrombin
Fibrin formation
Initiation of coagulation cascade
Regulation of clotting cascade
Amplification and propagation of coagulation cascade

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.

FGAF5SERPIN…FGBFGGSERPIN…F10THBDF2RF3F2

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

1

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.

dabigatran
Narrow target profileApprovedInhibitor

Thrombin inhibitor

Appears in clinical studies involving Stroke, Paroxysmal atrial fibrillation, Thrombocytopenia, atrial fibrillation

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.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

congenital prothrombin deficiency0.94

Genetic · overall 0.82

prothrombin deficiency0.93

Genetic · overall 0.66

thrombophilia due to thrombin defect0.89

Genetic · overall 0.74

deep vein thrombosis0.89

Genetic · overall 0.67

Congenital factor II deficiency0.88

Genetic · overall 0.80

Highest-confidence therapeutic associations

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

venous thromboembolism0.90

Clinical · overall 0.71

blood coagulation disease0.88

Clinical · overall 0.67

pulmonary embolism0.76

Clinical · overall 0.64

ischemic stroke0.74

Clinical · overall 0.67

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

hereditary thrombophilia due to congenital protein C deficiency0.60

Genetic literature

Show all associations
congenital prothrombin deficiency0.82
Congenital factor II deficiency0.80
thrombophilia due to thrombin defect0.74
venous thromboembolism0.71
deep vein thrombosis0.67
blood coagulation disease0.67
ischemic stroke0.67
prothrombin deficiency0.66
pulmonary embolism0.64
hereditary thrombophilia due to congenital protein C deficiency0.60

Open Targets ranks 1,484 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 · 14 total

ARGATROBANApproval

Thrombocytopenia · Recurrent thrombophlebitis · thrombotic disease

DABIGATRANApproval

Stroke · Paroxysmal atrial fibrillation · Thrombocytopenia

BIVALIRUDINApproval

Thrombocytopenia · thrombotic disease · Recurrent thrombophlebitis

XIMELAGATRANApproval

Recurrent thrombophlebitis · blood coagulation disease · atrial fibrillation

DABIGATRAN ETEXILATEApproval

ischemic stroke · atrial fibrillation · Recurrent thrombophlebitis

PROTHROMBIN COMPLEX CONCENTRATEPhase 3

blood coagulation disease · Multiple Organ Failure · cardiac transplant

LEPIRUDINApproval

Recurrent thrombophlebitis · Thrombocytopenia · Thromboembolism

DEFIBROTIDEApproval

Recurrent thrombophlebitis · hepatic veno-occlusive disease · diabetic kidney disease

ICHORCUMABPhase 1

thrombotic disease

PROTHROMBINApproval

blood coagulation disease

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · Advanced ClinicalAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Half-life DataPR · Small Molecule BinderOC · Approved Drug

Safety liabilities

Impaired recruitment , Population trajectorydeep vein thrombosishemorrhagic events

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.

Prospective Study on the Impact of Different Anti-thrombotic Therapies on Subclinical Leaflet Thickening and Its Temporal Dynamics in Transcatheter Bioprosthetic Aortic Valves (NOTION-4)NA

ACTIVE_NOT_RECRUITING · via dabigatran · NCT06449469

Oral Anticoagulation After Cardiac Surgery in the Era of Direct Oral Anticoagulants: is Large Use of Vitamin K Antagonists Still Justified?PHASE2

WITHDRAWN · via dabigatran · NCT04002011

Dabigatran vs. Oral Anti-Xa Inhibitors in S. Aureus BacteremiaPHASE4

RECRUITING · via dabigatran · NCT06650501

Open-label, Single Dose, Tolerability, Pharmacokinetic/Pharmacodynamics and Safety Study of Dabigatran Etexilate Given at the End of Standard Anticoagulant Therapy in Children Aged Less Than 1 Year OldPHASE2

COMPLETED · via dabigatran · NCT02223260

Direct Oral Anticoagulants (DOACs) Versus LMWH +/- Warfarin for VTE in Cancer: A Randomized Effectiveness Trial (CANVAS Trial)NA

COMPLETED · via dabigatran · NCT02744092

Double-Blind, Randomized, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of LT3001 Drug Product and Drug-Drug Interaction in Healthy Adult SubjectsPHASE1

COMPLETED · via dabigatran · NCT04809818

Show remaining trials (24)
Relative Bioavailability of Dabigatran and Atorvastatin After 150 mg BID Dabigatran Etexilate and Atorvastatin at 80 mg QD Alone or Following Concomitant Multiple Oral Administrations in Healthy Male and Female Volunteers (an Open-label, Randomised, Multiple-dose, Three-way Crossover Study)PHASE1

COMPLETED · via dabigatran · NCT02171039

Pilot-Trial: Dabigatran as an Alternative Anticoagulant in Patients With Left Ventricular Assist DevicePHASE2

TERMINATED · via dabigatran · NCT02872649

Prospective Randomized Study for Evaluating Vascular Protective Effects of New Oral Anticoagulants in High Risk Patients With Atrial FibrillationPHASE3

UNKNOWN · via dabigatran · NCT02544932

Prevention of Silent Cerebral Thromboembolism by Oral Anticoagulation With Dabigatran After Pulmonary Vein Isolation for Atrial FibrillationPHASE4

COMPLETED · via dabigatran · NCT02067182

Dabigatran Following Transient Ischemic Attack and Minor StrokePHASE2

COMPLETED · via dabigatran · NCT02295826

Comparison of Blood Loss Following Total Hip Arthroplasty With the Use of Three Thromboprophylactic Regimes: Dabigatran, Enoxaparin and Rivaroxaban.NA

UNKNOWN · via dabigatran · NCT02085824

Effect of Inhibitors of the Proton Pump on Intestinal Transporters and Their Impact on the Pharmacokinetics of Dabigatran - Mechanistic and Clinical Approach -BIPP StudyPHASE1

COMPLETED · via dabigatran · NCT02524210

Study on the Pharmacokinetics and Point of Care Testing After a Single Dose of 150 mg Dabigatran, 20 mg Rivaroxaban, 5 mg Apixaban, and 60 mg Edoxaban in Healthy Male SubjectsPHASE1

UNKNOWN · via dabigatran · NCT05491460

Pharmacodynamic Effects of Dabigatran in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy With Aspirin and ClopidogrelNA

COMPLETED · via dabigatran · NCT01852162

Efficacy and Safety of Dabigatran in Patients With Cirrhosis and Portal Vein Thrombosis-A Randomized Placebo Controlled TrialNA

UNKNOWN · via dabigatran · NCT04433481

Randomized Clinical Trial for the Prevention of Cognitive Impairment in Atrial Fibrillation Patients Treated With Dabigatran or WarfarinPHASE4

COMPLETED · via dabigatran · NCT01994265

Relative Bioavailability of Single Oral Doses of 150 mg Dabigatran Etexilate With or Without Oral Administration of Verapamil in Two Different Dosages (240 mg and 480 mg Daily) (Open-label, Fixed-sequence Design), and Relative Bioavailability of Single Oral Doses of 150 mg Dabigatran Etexilate Given With or Without Single Oral Doses of 120 mg (IR) or 240 mg (ER) of Verapamil Administered at Different Time Points Relative to Dabigatran Etexilate Dosing in Healthy Male and Female Volunteers (Open-label, Randomised, Five-way Crossover Design, Phase I Study)PHASE1

COMPLETED · via dabigatran · NCT02171533

Start or STop Anticoagulants Randomised Trial (SoSTART) After Spontaneous Intracranial HaemorrhagePHASE3

COMPLETED · via dabigatran · NCT03153150

Dabigatran Versus Warfarin After Mitral and Aortic Bioprosthesis Replacement for the Management of Atrial Fibrillation Postoperatively: Pilot StudyPHASE2/PHASE3

TERMINATED · via dabigatran · NCT01868243

Randomised, Double-blind Within Dose Groups, Placebo-controlled Phase I Trial in Healthy Japanese Male Volunteers to Investigate Safety, Tolerability and Pharmacokinetics of Different Doses of BI 655075 (Part 1) and to Explore the Effective Dose of BI 655075 to Reverse Dabigatran Anticoagulant Activity (Part 2).PHASE1

COMPLETED · via dabigatran · NCT02028780

Pharmacokinetics, Safety and Pharmacodynamics After Multiple Oral Doses of Dabigatran Etexilate Capsule (110 mg and 150 mg b.i.d., 7 Days) in Healthy Japanese and Caucasian Male Subjects (Open Label Study)PHASE1

COMPLETED · via dabigatran · NCT02171468

Compare the Efficacy and Safety of Dabigatran and Enoxaparin in Patients With Portal Vein Thrombosis With Cirrhosis: A Randomized Controlled StudyPHASE2/PHASE3

NOT_YET_RECRUITING · via dabigatran · NCT06818279

Randomised, Open Label, 3-way Cross Over Phase I Study to Investigate the Impact of Concomitant Use of Multiple Doses of Clopidogrel (75 mg qd After a Loading Dose of 300 mg) With Multiple Doses of Dabigatran Etexilate (150 mg Bid) on the Pharmacokinetic and Pharmacodynamic Parameters, and Additionally the Impact of Single Oral Doses of 300 mg and 600 mg of Clopidogrel Administered Under Steady State Conditions of Dabigatran of 75 mg and 150 mg in Healthy Male SubjectsPHASE1

COMPLETED · via dabigatran · NCT02171598

Phase II, Randomized, Crossover, Single Blind, Safety Trial of DABIGATRAN Versus ASA for Preventing Ischaemic Brain Lesions in Patients Affected by CADASILPHASE2

UNKNOWN · via dabigatran · NCT01361763

A 24-month, Randomized-control, Double-blind, Multi-center, Delayed-start, Pilot Study Evaluating Thrombin Inhibitions Alzheimer's Disease Using 150mg Dabigatran Daily: A Novel Therapeutic Target for Alzheimer's DiseasePHASE1

WITHDRAWN · via dabigatran · NCT03752294

An Open-Label, Randomized, 2-Period Crossover Study To Evaluate The Effect Of A Single Oral Dose Of Bosutinib On The Pharmacokinetics Of Dabigatran Etexilate Mesylate Administered Orally To Healthy SubjectsPHASE1

COMPLETED · via dabigatran · NCT02102633

The Safety and Pharmacodynamics of Two Doses of Dabigatran Etexilate in Patients Undergoing Cardiac CatheterizationPHASE2

COMPLETED · via dabigatran · NCT00818753

A PHASE 1, RANDOMIZED, 2-WAY CROSSOVER, SINGLE DOSE, OPEN LABEL STUDY TO ESTIMATE THE EFFECT OF PF-04965842 ON DABIGATRAN PHARMACOKINETICS IN HEALTHY PARTICIPANTSPHASE1

COMPLETED · via dabigatran · NCT03742336

Investigating the Role of the Coagulation Cascade in Idiopathic Pulmonary FibrosisNA

UNKNOWN · via dabigatran · NCT02885961

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.

deep vein thrombosisWell supported
0.96
agreement 0.85–1.00
Genetic56%Clinical39%Literature5%

Open Targets aggregate 0.67 · 3 independent evidence families

blood coagulation diseaseWell supported
0.95
agreement 0.84–1.00
Genetic55%Clinical43%Literature2%

Open Targets aggregate 0.67 · 3 independent evidence families

congenital prothrombin deficiencyWell supported
0.95
agreement 0.83–1.00
Genetic90%Animal model10%Literature0%Genetic literaturedup

Open Targets aggregate 0.82 · 3 independent evidence families · 1 not counted as duplicate

pulmonary embolismWell supported
0.94
agreement 0.83–1.00
Genetic58%Clinical39%Literature3%

Open Targets aggregate 0.64 · 3 independent evidence families

venous thromboembolismWell supported
0.93
agreement 0.83–1.00
Genetic52%Clinical45%Literature4%

Open Targets aggregate 0.71 · 3 independent evidence families

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

What's happening now

3

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

  1. New publication2021-10-01
    2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation.

    Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2021 · 670 citations · Europe PMC · via dabigatran

  2. Safety communication2014-12-11

    Drug Safety Update: Dabigatran (Pradaxa▼): risk of serious haemorrhage

    mhra · safety · mhra · via dabigatran

  3. Safety communication2014-12-11

    Drug Safety Update: Dabigatran (Pradaxa): contraindicated in patients with prosthetic heart valve(s) requiring anti-coagulant treatment

    mhra · safety · mhra · via dabigatran

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.