Vorapaxar

Summary

Vorapaxar (CHEMBL493982) is an approved small-molecule protease-activated receptor-1 antagonist (ATC B01AC26) targeting F2R; indicated across 3 conditions including thrombotic disease and cerebral infarction.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: B01AC26
• Targets: 1 (F2R)
• Indications: 3 conditions
• Clinical trials: 12
• Chemistry: 492.6 Da · C29H33FN2O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL493982
Name	Vorapaxar
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	10077130
ChEBI	CHEBI:82702
ATC	B01AC26
Molecular formula	C29H33FN2O4
Molecular weight	492.6
InChIKey	ZBGXUVOIWDMMJE-QHNZEKIYSA-N

SMILES: CCOC(=O)N[C@@H]1CC[C@@H]2[C@@H](C1)C[C@@H]3[C@H]([C@H]2/C=C/C4=NC=C(C=C4)C5=CC(=CC=C5)F)[C@H](OC3=O)C

IUPAC name: ethyl N-[(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]-1-methyl-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]carbamate

ChEBI definition: A carbamate ester that is the ethyl ester of [(1R,3aR,4aR,6R,8aR,9S,9aS)-9-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]ethynyl}-1-methyl-3-oxododecahydronaphtho[2,3-c]furan-6-yl]carbamic acid. A protease-activated receptor-1 antagonist used (as its sulfate salt) for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease. It has been shown to reduce the rate of a combined endpoint of cardiovascular death, MI, stroke and urgent coronary revascularisation.

Pharmacological roles (ChEBI): protease-activated receptor-1 antagonist, platelet aggregation inhibitor, cardiovascular drug.

Also known as: Vorapaxar, vorapaxar, VORAPAXAR, C0088673

Parent form; salt/anhydrous children: CHEMBL2107386, CHEMBL3542336

Patent coverage: 424 distinct patent families (1,021 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
F2R	PAR1	Antagonist	8.09	2.2%	P25116

Broader ChEMBL bioactivity targets: 10 (assay-derived). Sample: G-protein coupled receptor 35, Muscarinic acetylcholine receptor M1, Sodium-dependent noradrenaline transporter, Mu-type opioid receptor, Voltage-gated inwardly rectifying potassium channel KCNH2, Adenosine receptor A3, G-protein coupled receptor 183, Proteinase-activated receptor 1, Synaptic vesicular amine transporter, Bile salt export pump.

Bioactivity

ChEMBL activities: 22 potent at pChembl ≥ 5 of 23 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
F2R	8.96	IC50	1.1	nM	CHEMBL_ACT_13849940
F2R	8.96	Ki	1.1	nM	CHEMBL_ACT_2357058
F2R	8.82	IC50	1.5	nM	CHEMBL_ACT_13849930
F2R	8.1	Ki	8	nM	CHEMBL_ACT_3519479
F2R	8.09	Ki	8.1	nM	CHEMBL_ACT_2357029
F2R	8.07	Ki	8.5	nM	CHEMBL_ACT_13891690
F2R	7.89	Ki	13	nM	CHEMBL_ACT_2357059
F2R	7.6	IC50	25	nM	CHEMBL_ACT_2357080
F2R	7.51	IC50	31	nM	CHEMBL_ACT_18186603
F2R	7.33	IC50	47	nM	CHEMBL_ACT_2357081
F2R	7.19	IC50	64	nM	CHEMBL_ACT_18186584
F2R	7.09	IC50	81	nM	CHEMBL_ACT_18186606
F2R	6.92	IC50	120	nM	CHEMBL_ACT_13849923
F2R	6.6	IC50	250	nM	CHEMBL_ACT_20707429
OPRM1	6.09	AC50	820.2	nM	CHEMBL_ACT_25158465
Q01827	5.89	AC50	1300	nM	CHEMBL_ACT_25197382
ABCB11	5.66	AC50	2200	nM	CHEMBL_ACT_25127105
ADORA3	5.62	AC50	2429	nM	CHEMBL_ACT_25198947
KCNH2	5.41	AC50	3900	nM	CHEMBL_ACT_25118183
SLC6A2	5.34	AC50	4555	nM	CHEMBL_ACT_25146290
GPR183	5.32	IC50	4765	nM	CHEMBL_ACT_25751471
GPR35	5.12	IC50	7574	nM	CHEMBL_ACT_25751472

Target pathways

Aggregated over 1 target gene(s): F2R.

Top Reactome pathways

5 total, by targets touching each:

Pathway	Targets	Genes
R-HSA-140875	1	F2R
Peptide ligand-binding receptors	1	F2R
G alpha (q) signalling events	1	F2R
Thrombin signalling through proteinase activated receptors (PARs)	1	F2R
Regulation of clotting cascade	1	F2R

Dominant GO biological processes

GO term	Targets
connective tissue replacement involved in inflammatory response wound healing	1
negative regulation of glomerular filtration	1
inflammatory response	1
G protein-coupled receptor signaling pathway	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
positive regulation of cytosolic calcium ion concentration	1
establishment of synaptic specificity at neuromuscular junction	1
positive regulation of cell population proliferation	1
negative regulation of cell population proliferation	1
response to wounding	1
anatomical structure morphogenesis	1
platelet activation	1
regulation of blood coagulation	1
positive regulation of blood coagulation	1
positive regulation of cell migration	1

Indications & clinical

Indications

3 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
thrombotic disease	4	MONDO:0000831	HP:0004419
cerebral infarction	2	MONDO:0002679	MONDO:0002679
HIV infectious disease	1	MONDO:0005109	EFO:0000764

Clinical trials

Total trials: 12.

Phase distribution

Phase	Trials
PHASE4	6
PHASE3	3
PHASE2	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02545933	PHASE4	COMPLETED	Vorapaxar in Patients With Prior Myocardial Infarction Treated With Prasugrel and Ticagrelor
NCT02548650	PHASE4	COMPLETED	Vorapaxar as an Add-On Antiplatelet Therapy in Patients With and Without Diabetes Mellitus
NCT02660866	PHASE4	UNKNOWN	Excellence In Peripheral Artery Disease Thrombin Receptor Antagonist Intervention In Claudication Evaluation (XLPAD-TRACE Trial)
NCT02875028	PHASE4	COMPLETED	Vorapaxar in the Human Endotoxemia Model
NCT02975583	PHASE4	WITHDRAWN	Vorapaxar and Lower Extremity Bypass Grafts
NCT03207451	PHASE4	COMPLETED	Vorapaxar on Thrombin Generation and Coagulability
NCT00526474	PHASE3	COMPLETED	Trial to Assess the Effects of Vorapaxar (SCH 530348; MK-5348) in Preventing Heart Attack and Stroke in Patients With Atherosclerosis (TRA 2°P - TIMI 50) (P04737)
NCT00527943	PHASE3	TERMINATED	Trial to Assess the Effects of Vorapaxar (SCH 530348; MK-5348) in Preventing Heart Attack and Stroke in Particpants With Acute Coronary Syndrome (TRA•CER) (Study P04736)
NCT00617123	PHASE3	COMPLETED	Trial to Assess the Ocular Safety of Vorapaxar (SCH 530348) in Participants With Atherosclerosis (Study P05183)
NCT00684203	PHASE2	COMPLETED	Trial to Assess the Safety and Effects of Vorapaxar in Japanese Subjects With Acute Coronary Syndrome (P04772; MK-5348-016)
NCT00684515	PHASE2	COMPLETED	Trial to Assess the Safety of Vorapaxar in Japanese Subjects With Cerebral Infarction (P05005; MK-5348-017)
NCT02394730	PHASE1/PHASE2	COMPLETED	Attenuation of D-dimer Using Vorapaxar to Target Inflammatory and Coagulation Endpoints

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

1 molecules share ≥1 primary target. Top 1 by shared-target count:

Molecule	Source	Status	Shared targets
ATOPAXAR	ChEMBL	Phase 2	F2R