Thrombin Inhibitors
8 drugsAbout Thrombin
Thrombin (F2), a serine protease in the coagulation cascade, converts fibrinogen to fibrin, forming blood clots and playing a key role in hemostasis and thrombosis.
Human genetics strongly support Thrombin as a target, with variants linked to congenital prothrombin deficiency (score 0.94) and deep vein thrombosis (score 0.91); loss-of-function is protective.
Six FDA-approved small molecule drugs target Thrombin, including Dabigatran etexilate mesylate, Argatroban, and Bivalirudin, primarily for cardiovascular indications.
Thrombin Genetic Evidence Strong
Strong genetic evidence links Thrombin to 42 diseases, with a max score of 0.94 for congenital prothrombin deficiency.
The strong genetic support suggests that clinical trials targeting genetically validated indications have a higher probability of success.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 67% directional consistency across 3 traits
- • Strong signal in hematologic disease, genetic, familial or congenital disease pathways
Cross-Disease Effects
Trade-off: ModerateDirection of Effect
67% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link F2 to 42 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for F2 colocalize with these GWAS traits, providing causal evidence that gene expression changes drive disease risk.
Understanding these scores
Association Score (0-1): Combines all evidence types (genetic, literature, drugs, animal models). Higher = more evidence linking target to disease. This is a ranking heuristic, not a confidence score.
L2G Score: Open Targets uses a machine learning model (Locus-to-Gene) to predict which gene is causal at each GWAS locus. L2G=0.5 means ~50% probability of being the causal gene. Only associations with L2G > 0.05 are included.
Odds Ratio (OR): From gene burden studies (UK Biobank, AstraZeneca PheWAS). Measures how loss-of-function variants affect disease risk. OR<1 = protective (inhibiting target may help), OR>1 = risk (losing function causes disease).
Beta (β): Effect size for continuous traits. β<0 = protective, β>0 = risk.
Clinical Translation (~1.8x): Based on Nelson et al. 2015: drug targets with genetic evidence have ~2x higher success rates in clinical trials. We estimate: Strong support (score ≥0.7) → ~1.8x, Moderate (0.3-0.7) → ~1.3x, Weak → baseline.
Colocalization (H4): Tests whether a GWAS signal and an eQTL/pQTL signal share the same causal variant. H4 is the posterior probability that both traits are associated AND share a causal variant. H4 > 0.8 = strong evidence that gene expression/protein levels drive disease risk. This links genetic variation → gene expression → disease, supporting the target-disease connection.
Top Thrombin Drugs
Six companies have approved Thrombin-targeting drugs, with Hetero Labs Ltd III leading with Dabigatran etexilate mesylate.
The relatively low number of companies suggests moderate barriers to entry, but also potential for market disruption.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| BIVALIRUDIN | Viatris | 2015 | 2 |
| ANGIOMAX RTU | MAIA PHARMS INC | 2019 | 2 |
| PRADAXA | Boehringer Ingelheim | 2010 | 1 |
| HEPARIN SODIUM | SOLOPAK | 1939 | - |
| HEPARIN SODIUM PRESERVATIVE FREE | Fresenius Kabi | 1943 | - |
Thrombin Drug Modality Landscape
Modalities
Routes of Administration
Thrombin is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or peptides could offer a competitive advantage in targeting Thrombin.
Thrombin Clinical Trials 142 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Thrombin. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 56 | 48 | 4 | 4 | 92% |
| Phase 2 | 19 | 9 | 6 | 4 | 60% |
| Phase 3 | 22 | 17 | 5 | 0 | 77% |
| Phase 4 | 45 | 27 | 12 | 6 | 69% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Thrombin Drug Approval Timeline (2000 - 2020)
The first Thrombin inhibitor was approved in 2000 (Argatroban), with the most recent approval in 2020 (Dabigatran etexilate mesylate).
The approval timeline indicates continued interest in Thrombin as a target, but also suggests a potentially saturated market.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 7 companies competing
- • Market share by company
Full Drug Portfolio
- • All 8 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 8-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 93 (26 companies)
- • Completion rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Count Trials
- Trials: phase 1-4 interventional trials on ClinicalTrials.gov that started in 2008 or later and test an FDA-approved drug acting on Thrombin. A trial counts if an approved drug acting on Thrombin is in any arm, including as a comparator, and a trial that tests two such drugs counts once. Trials that test only unapproved drugs are not counted. A trial listed as phase 1/2 counts as phase 1, and phase 2/3 as phase 2.
- Active: recruiting, not yet recruiting, enrolling by invitation, or active and no longer recruiting.
- Completion rate: of the trials that have ended, the share marked Completed rather than Terminated or Withdrawn. Completed means the trial ended as planned; it does not mean the drug worked. Suspended trials are not counted as ended.
- Stopped: terminated or withdrawn. Trials stop for many reasons, including slow enrolment and business decisions, not only safety or efficacy.
- Sponsors: the lead sponsor of each trial. Companies are the sponsors ClinicalTrials.gov classes as industry; the rest are universities, hospitals, cooperative groups, government bodies and individuals.