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

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

  • Status: ONP

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

Drug dosage:

None

ADMET properties:

None

Approvals:

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

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
Recurrent cancer 496.03 30.55 93 4344 1666 46679959
Carbohydrate antigen 125 increased 360.21 30.55 75 4362 2335 46679290
Intentional underdose 289.01 30.55 60 4377 1838 46679787
Disease progression 259.98 30.55 140 4297 91160 46590465
Platelet count decreased 231.82 30.55 134 4303 99890 46581735
Thrombocytopenia 160.14 30.55 116 4321 126465 46555160
Constipation 97.24 30.55 100 4337 173997 46507628
Nausea 73.48 30.55 184 4253 687270 45994355
Ovarian cancer recurrent 60.88 30.55 15 4422 996 46680629
Red blood cell count decreased 57.97 30.55 37 4400 32586 46649039
Insomnia 55.35 30.55 73 4364 164851 46516774
Emotional distress 54.99 30.55 35 4402 30672 46650953
Fatigue 54.70 30.55 153 4284 608544 46073081
Eastern Cooperative Oncology Group performance status worsened 51.10 30.55 11 4426 400 46681225
Haemoglobin decreased 46.23 30.55 59 4378 128890 46552735
Tumour marker increased 46.15 30.55 16 4421 3525 46678100
Blood pressure increased 40.81 30.55 55 4382 126611 46555014
Blood count abnormal 38.67 30.55 23 4414 17855 46663770
Malignant neoplasm progression 37.36 30.55 38 4399 64888 46616737
Intentional product misuse 35.49 30.55 32 4405 47096 46634529
Ovarian cancer metastatic 33.76 30.55 9 4428 817 46680808
Myelodysplastic syndrome 33.43 30.55 20 4417 15691 46665934
Acute myeloid leukaemia 33.35 30.55 20 4417 15758 46665867
Eastern Cooperative Oncology Group performance status 33.05 30.55 4 4433 0 46681625
Dry mouth 31.32 30.55 32 4405 54894 46626731
Heart rate increased 31.25 30.55 37 4400 74754 46606871

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 L01XK02 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Poly (ADP-ribose) polymerase (PARP) inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D000067856 Poly(ADP-ribose) Polymerase Inhibitors
FDA MoA N0000191622 Poly(ADP-Ribose) Polymerase Inhibitors
FDA EPC N0000191623 Poly(ADP-Ribose) Polymerase Inhibitor

Drug Use (View source of the data)

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

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)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 100MG BASE ZEJULA GLAXOSMITHKLINE N208447 March 27, 2017 RX CAPSULE ORAL March 27, 2022 NEW CHEMICAL ENTITY
EQ 100MG BASE ZEJULA GLAXOSMITHKLINE N208447 March 27, 2017 RX CAPSULE ORAL Oct. 23, 2022 TX OF ADULT PTS W/ ADV OVARIAN FALLOPIAN TUBE OR PRIMARY PERITONEAL CANCER TREATED W/ >=3 PRIOR CHEMO REGIMENS & ASSOCIATED W/ HRD DEFICIENCY POSITIVE STATUS DEFINED BY A DELETERIOUS OR SUSPECTED DELETERIOUS BRCA MUTATION
EQ 100MG BASE ZEJULA GLAXOSMITHKLINE N208447 March 27, 2017 RX CAPSULE ORAL Oct. 23, 2022 TX OF ADV OVARIAN FALLOPIAN TUBE OR PRIMARY PERITONEAL CANCER TREATED W/ >=3 PRIOR CHEMO REGIMENS & ASSOCIATED W/ HRD DEFICIENCY DEFINED BY POSITIVE STATUS GENOMIC INSTABILITY & WHO HAVE PROGRESSED >6MO AFTER RESPONSE TO LAST PLATINUM-BASED CHEMO
EQ 100MG BASE ZEJULA GLAXOSMITHKLINE N208447 March 27, 2017 RX CAPSULE ORAL April 29, 2023 MAINTENULLNCE TREATMENT OF ADULT PATIENTS WITH ADVANCED EPITHELIAL OVARIAN, FALLOPIAN TUBE, OR PRIMARY PERITONEAL CANCER WHO ARE IN A COMPLETE OR PARTIAL RESPONSE TO FIRST-LINE PLATINUM-BASED CHEMOTHERAPY
EQ 100MG BASE ZEJULA GLAXOSMITHKLINE N208447 March 27, 2017 RX CAPSULE ORAL March 27, 2024 INDICATED FOR MAINTENULLNCE 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
EQ 100MG BASE ZEJULA GLAXOSMITHKLINE N208447 March 27, 2017 RX CAPSULE ORAL Oct. 23, 2026 TX OF ADULTS W/ ADV OVARIAN, FALLOPIAN TUBE, OR PRIMARY PERITONEAL CANCER TREATED W/ >=3 PRIOR CHEMO REGIMENS & CANCER ASSOCIATED W/ HRD+ STATUS DEFINED BY A DELETERIOUS OR SUSPECTED DELETERIOUS BRCA MUTATION
EQ 100MG BASE ZEJULA GLAXOSMITHKLINE N208447 March 27, 2017 RX CAPSULE ORAL Oct. 23, 2026 TX OF ADULTS W/ ADV OVARIAN, FALLOPIAN TUBE, OR PRIMARY PERITONEAL CANCER TREATED W/ >=3 PRIOR CHEMO REGIMENS & CANCER ASSOCIATED W/ HRD+ STATUS DEFINED BY GENOMIC INSTABILITY & PROGRESSED >6 MONTHS AFTER RESPONSE TO THE LAST PLATINUM-BASED CHEMOTHERAPY
EQ 100MG BASE ZEJULA GLAXOSMITHKLINE N208447 March 27, 2017 RX CAPSULE ORAL April 29, 2027 INDICATED FOR THE MAINTENULLNCE TREATMENT OF ADULT PATIENTS WITH ADVANCED EPITHELIAL OVARIAN CANCER WHO ARE IN A COMPLETE OR PARTIAL RESPONSE TO FIRST-LINE PLATINUM-BASED CHEMOTHERAPY

Bioactivity Summary:

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:

IDSource
1038915-64-8 SECONDARY_CAS_RN
4036640 VANDF
C2744441 UMLSCUI
3JD PDB_CHEM_ID
CHEMBL1094636 ChEMBL_ID
CHEMBL3989922 ChEMBL_ID
D10140 KEGG_DRUG
DB11793 DRUGBANK_ID
C545685 MESH_SUPPLEMENTAL_RECORD_UI
8275 IUPHAR_LIGAND_ID
9526 INN_ID
HMC2H89N35 UNII
24958200 PUBCHEM_CID
1918231 RXNORM
254987 MMSL
32539 MMSL
d08539 MMSL
017145 NDDF
017146 NDDF
391000220105 SNOMEDCT_US
733733005 SNOMEDCT_US
763561009 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ZEJULA HUMAN PRESCRIPTION DRUG LABEL 1 69656-103 CAPSULE 100 mg ORAL NDA 30 sections