F2R coagulation factor II thrombin receptor
ENSG00000181104 · protein coding · Open Targets profile
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). {ECO:0000250|UniProtKB:P26824, ECO:0000250|UniProtKB:P30558, ECO:0000269|PubMed:10079109, ECO:0000269|PubMed:1672265, ECO:0000269|PubMed:30568593, ECO:0000269|PubMed:34831181, ECO:0000269|PubMed:8136362}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, Druggable Family
- Antibody
- GO CC high conf, UniProt loc med conf, UniProt SigP or TMHMM
- PROTAC
- Database Ubiquitination, Small Molecule Binder
- Other modalities
- Advanced Clinical
gnomAD loss of function constraint: o/e 0.6571099758148193 (upper bound 1.0647000074386597). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 1 registry trials, updated in the last three years, of the most advanced drugs against F2R (vorapaxar, PZ-128, atopaxar), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Athan KuliopulosTufts Medical Center · 1 of 1 trials Phase 2+
Registry trials of vorapaxar, PZ-128, atopaxar updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 1 of 1 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. Source: ClinicalTrials.gov, fetched live.
2 trials of drugs against F2R were stopped early
Terminated, withdrawn and suspended interventional trials of vorapaxar, PZ-128, atopaxar, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 2 most recent of 2.
- terminated · 2018-09-21 · Merck Sharp & Dohme LLC · Vorapaxar“The trial was terminated at the request of the Data and Safety Monitoring Board.”
- withdrawn · 2018-01-25 · Vanderbilt University · Vorapaxar“We could not secure adequate medication”
Paediatric incentives and obligations for F2R's drugs
For vorapaxar, PZ-128, atopaxar: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · F2R is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMEA-000778-PIP02-12-M01 (vorapaxar, Prevention of arterial thromboembolism): PM: decision on the application for modification of an agreed PIP, 20 May 2016Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA EMEA-000778-PIP02-12-M01, 2026-11-11
- EU orphan designation: no · No EU orphan designation names vorapaxar, pz-128, atopaxarRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: no · Zontivity: withdrawn since 19 Jan 2015Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA EPAR Zontivity, 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of vorapaxar, pz-128, atopaxarRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: no · No interventional study of vorapaxar, pz-128, atopaxar includes patients under 18Rule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-12
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 4 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.
| Drug | Type | Highest stage | Indications | Source records |
|---|---|---|---|---|
| VORAPAXAR SULFATE | Small molecule | approval | myocardial infarction, peripheral arterial disease, stroke disorder | Open Targets · ChEMBL |
| PZ-128 | Protein | phase 2 | Myocardial necrosis, acute coronary syndrome, coronary artery disorder | Open Targets · ChEMBL |
| ATOPAXAR | Small molecule | phase 2 | acute coronary syndrome, coronary artery disorder | Open Targets · ChEMBL |
| VORAPAXAR | Small molecule | withdrawal | myocardial infarction, Recurrent thrombophlebitis, ischemic stroke, blood coagulation disease, inflammation, HIV infectious disease | Open Targets · ChEMBL |