vorapaxar Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
4870 618385-01-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • SCH-530348
  • SCH530348
  • vorapaxar
  • vorapaxar sulfate
  • zontivity
  • SCH 530348
Vorapaxar is a reversible antagonist of the protease-activated receptor-1 (PAR-1) expressed on platelets, but its long half-life makes it effectively irreversible. Vorapaxar inhibits thrombin-induced and thrombin receptor agonist peptide (TRAP)-induced platelet aggregation in vitro studies. Vorapaxar does not inhibit platelet aggregation induced by adenosine diphosphate (ADP), collagen or a thromboxane mimetic and does not affect coagulation parameters ex vivo. PAR-1 receptors are also expressed in a wide variety of cell types, including endothelial cells, neurons, and smooth muscle cells, but the pharmacodynamic effects of vorapaxar in these cell types have not been assessed.
  • Molecular weight: 492.59
  • Formula: C29H33FN2O4
  • CLOGP: 4.34
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 1
  • TPSA: 77.52
  • ALOGS: -5.88
  • ROTB: 6

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
2.08 mg O

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 3.74 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 0.34 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.01 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 149 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Nov. 20, 2014 EMA Merck Sharp & Dohme Limited
May 8, 2014 FDA MERCK SHARP DOHME

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Diarrhoea 8.74 0 3 11 83561 2274510

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event

Pharmacologic Action:

SourceCodeDescription
ATC B01AC26 BLOOD AND BLOOD FORMING ORGANS
ANTITHROMBOTIC AGENTS
ANTITHROMBOTIC AGENTS
Platelet aggregation inhibitors excl. heparin
MeSH PA D006401 Hematologic Agents
MeSH PA D010975 Platelet Aggregation Inhibitors
CHEBI has role CHEBI:50427 platelet aggregation inhibitor
CHEBI has role CHEBI:35554 cardiovascular drug
FDA EPC N0000190996 Protease-activated Receptor-1 Antagonist
FDA MoA N0000190995 Protease-activated Receptor-1 Antagonists

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Cerebrovascular accident indication 230690007
Myocardial Infarction Prevention indication
Transient ischemic attack contraindication 266257000 DOID:224
Cerebral hemorrhage contraindication 274100004

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 3.9 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 2.08MG BASE ZONTIVITY TOPROL N204886 May 8, 2014 RX TABLET ORAL 7304078 April 6, 2024 REDUCTION OF THROMBOTIC CARDIOVASCULAR EVENTS
EQ 2.08MG BASE ZONTIVITY TOPROL N204886 May 8, 2014 RX TABLET ORAL 7713999 May 30, 2024 REDUCTION OF THROMBOTIC CARDIOVASCULAR EVENTS IN PATIENTS WITH A HISTORY OF MYOCARDIAL INFARCTION (MI) OR WITH PERIPHERAL ARTERIAL DISEASE (PAD)

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Proteinase-activated receptor 1 GPCR ANTAGONIST Ki 8.09 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE

External reference:

IDSource
D09765 KEGG_DRUG
4033329 VUID
N0000190755 NUI
C2974521 UMLSCUI
CHEMBL493982 ChEMBL_ID
IN66038E6C UNII
705260-08-8 SECONDARY_CAS_RN
VPX PDB_CHEM_ID
DB09030 DRUGBANK_ID
CHEBI:82702 CHEBI
8852 INN_ID
CHEMBL2107386 ChEMBL_ID
10077130 PUBCHEM_CID
4047 IUPHAR_LIGAND_ID
C530299 MESH_SUPPLEMENTAL_RECORD_UI
715596008 SNOMEDCT_US
1537034 RXNORM
d08260 MMSL
015526 NDDF
4033329 VANDF
708718003 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ZONTIVITY HUMAN PRESCRIPTION DRUG LABEL 1 70347-208 TABLET, FILM COATED 2.08 mg ORAL NDA 19 sections