niraparib indications/contra

Stem definitionDrug idCAS RN
poly-ADP-ribose polymerase inhibitors 5222 1038915-60-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • niraparib hydrochloride
  • niraparib HCl
  • MK-4827
  • niraparib
  • niraparib tosylate monohydrate
  • niraparib tosylate
  • zejula
Niraparib is an inhibitor of poly(ADP-ribose) polymerase (PARP) enzymes, PARP-1 and PARP-2, which play a role in DNA repair. In vitro studies have shown that niraparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis and cell death. Increased niraparib-induced cytotoxicity was observed in tumor cell lines with or without deficiencies in BRCA1/2. Niraparib decreased tumor growth in mouse xenograft models of human cancer cell lines with deficiencies in BRCA1/2 and in human patient-derived xenograft tumor models with homologous recombination deficiency that had either mutated or wild type BRCA1/2.
  • Molecular weight: 320.40
  • Formula: C19H20N4O
  • CLOGP: 2.72
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 2
  • TPSA: 72.94
  • ALOGS: -4.33
  • ROTB: 3

Drug dosage:

None

Approvals:

DateAgencyCompanyOrphan
Nov. 16, 2017 EMA Tesaro UK Limited
March 27, 2017 FDA TESARO INC

FDA Adverse Event Reporting System

scroll-->
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
Thrombocytopenia 106.55 49.01 28 135 35240 3350456
Platelet count decreased 98.27 49.01 25 138 27443 3358253
Nausea 89.12 49.01 33 130 129612 3256084
Constipation 76.24 49.01 21 142 30791 3354905

Pharmacologic Action:

scroll-->
SourceCodeDescription
ATC L01XX54 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Other antineoplastic agents
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D000067856 Poly(ADP-ribose) Polymerase Inhibitors
FDA EPC N0000191623 Poly(ADP-Ribose) Polymerase Inhibitor

Drug Use (View source of the data)

scroll-->
DiseaseRelationSNOMED_IDDOID
Carcinoma in situ of fallopian tube indication 92591008
Malignant epithelial tumor of ovary indication 254849005
Malignant tumor of peritoneum indication 363492001

Acid dissociation constants calculated using MoKa v3.0.0

scroll-->
Dissociation levelDissociation constantType (acidic/basic)
pKa1 10.95 acidic
pKa2 9.77 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

scroll-->
Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 100MG BASE ZEJULA TESARO INC N208447 March 27, 2017 RX CAPSULE ORAL March 27, 2022 NEW CHEMICAL ENTITY
EQ 100MG BASE ZEJULA TESARO INC N208447 March 27, 2017 RX CAPSULE ORAL March 27, 2024 INDICATED FOR MAINTENANCE TREATMENT OF ADULT PATIENTS WITH RECURRENT EPITHELIAL OVARIAN, FALLOPIAN TUBE, OR PRIMARY PERITONEAL CANCER WHO ARE IN A COMPLETE OR PARTIAL RESPONSE TO PLATINUM-BASED CHEMOTHERAPY

Bioactivity Summary:

scroll-->
TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Poly [ADP-ribose] polymerase 1 Enzyme INHIBITOR IC50 8.42 IUPHAR DRUG LABEL
Poly [ADP-ribose] polymerase 2 Enzyme INHIBITOR IC50 8.68 IUPHAR DRUG LABEL
Tankyrase-1 Enzyme IC50 6.24 CHEMBL
Poly [ADP-ribose] polymerase 4 Enzyme IC50 6.48 CHEMBL
Poly [ADP-ribose] polymerase 3 Enzyme IC50 5.89 CHEMBL

External reference:

scroll-->
IDSource
195Q483UZD UNII
1613220-15-7 SECONDARY_CAS_RN
CHEMBL1094636 ChEMBL_ID
D10140 KEGG_DRUG
8275 IUPHAR_LIGAND_ID
9526 INN_ID
C545685 MESH_SUPPLEMENTAL_RECORD_UI
1918231 RXNORM
017145 NDDF
d08539 MMSL
4036640 VANDF
733733005 SNOMEDCT_US
N0000193455 NDFRT
DB11793 DRUGBANK_ID
24958200 PUBCHEM_CID
3JD PDB_CHEM_ID

Pharmaceutical products:

scroll-->
ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
ZEJULA HUMAN PRESCRIPTION DRUG LABEL 1 69656-103 CAPSULE 100 mg ORAL NDA 17 sections