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Niraparib

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Also known as JNJ-64091742MK-4827MK4827ZejulaZL-2306MK 4827NIRAPARIB (MK-4827)[14C]-niraparibNireparib

Summary

Niraparib (CHEMBL1094636) is an approved small-molecule antineoplastic agent (ATC L01XK02) targeting PARP1 and PARP2; indicated across 43 conditions including neoplasm and ovarian carcinoma; with CIViC clinical evidence for 9 variant-indication associations (e.g. BRCA1 Mutation OR BRCA2 Mutation in epithelial ovarian cancer).

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: L01XK02
  • Targets: 2 (PARP1, PARP2)
  • Indications: 43 conditions
  • Clinical trials: 188
  • Precision-oncology evidence (CIViC): 9 variant–indication associations
  • Chemistry: 320.4 Da · C19H20N4O

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL1094636
NameNiraparib
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID24958200
ChEBICHEBI:176844
ATCL01XK02
Molecular formulaC19H20N4O
Molecular weight320.4
InChIKeyPCHKPVIQAHNQLW-CQSZACIVSA-N

SMILES: C1C[C@H](CNC1)C2=CC=C(C=C2)N3C=C4C=CC=C(C4=N3)C(=O)N

IUPAC name: 2-[4-[(3S)-piperidin-3-yl]phenyl]indazole-7-carboxamide

ChEBI definition: A 2-[4-(piperidin-3-yl)phenyl]-2H-indazole-7-carboxamide that has S-configuration. It is a potent inhibitor of PARP1 and PARP2 (IC50 of 3.8 and 2.1 nM, respectively) and approved as a first-line maintenance treatment for women with advanced ovarian cancer after responding to platinum-based chemotherapy.

Pharmacological roles (ChEBI): antineoplastic agent, EC 2.4.2.30 (NAD+ ADP-ribosyltransferase) inhibitor, radiosensitizing agent, apoptosis inducer.

Also known as: JNJ-64091742, MK-4827, MK4827, Niraparib, Zejula, ZL-2306, NIRAPARIB, MK 4827, ZEJULA, NIRAPARIB (MK-4827), niraparib, [14C]-niraparib

Parent form; salt/anhydrous children: CHEMBL3989922, CHEMBL5715247

Patent coverage: 2,707 distinct patent families (6,433 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).

GeneTargetActionpAffinityCancer dependencyUniProt
PARP1poly(ADP-ribose) polymerase 1Inhibition8.424.1%P09874
PARP2poly(ADP-ribose) polymerase 2Binding8.680.2%Q9UGN5

Broader ChEMBL bioactivity targets: 21 (assay-derived). Sample: Muscarinic acetylcholine receptor M2, Muscarinic acetylcholine receptor M1, Protein mono-ADP-ribosyltransferase PARP14, Protein mono-ADP-ribosyltransferase PARP15, Sodium-dependent noradrenaline transporter, Sodium-dependent serotonin transporter, Alpha-1A adrenergic receptor, Dual specificity tyrosine-phosphorylation-regulated kinase 1A, Sodium-dependent dopamine transporter, Voltage-gated inwardly rectifying potassium channel KCNH2.

Bioactivity

ChEMBL activities: 72 potent at pChembl ≥ 5 of 80 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
PARP19Kd1nMCHEMBL_ACT_24867465
PARP18.7IC502nMCHEMBL_ACT_15251058
PARP28.68IC502.1nMCHEMBL_ACT_19483603
PARP28.68IC502.1nMCHEMBL_ACT_24775566
PARP28.68IC502.1nMCHEMBL_ACT_25662127
PARP28.68IC502.1nMCHEMBL_ACT_29118521
PARP28.68IC502.1nMCHEMBL_ACT_3270465
PARP18.49Ki3.2nMCHEMBL_ACT_19483601
PARP18.49IC503.2nMCHEMBL_ACT_3270947
PARP18.46IC503.5nMCHEMBL_ACT_15251078
PARP18.42IC503.8nMCHEMBL_ACT_19441984
PARP18.42IC503.8nMCHEMBL_ACT_19483600
PARP18.42IC503.8nMCHEMBL_ACT_24775561
PARP18.42IC503.8nMCHEMBL_ACT_25662120
PARP18.42IC503.8nMCHEMBL_ACT_25898554
PARP18.42IC503.8nMCHEMBL_ACT_29118509
PARP18.4EC504nMCHEMBL_ACT_15251047
PARP18.4IC504nMCHEMBL_ACT_15251076
PARP28.4Ki4nMCHEMBL_ACT_19483604
PARP18.4EC504nMCHEMBL_ACT_3270565
PARP18.33IC504.67nMCHEMBL_ACT_25889177
PARP18.09IC508.05nMCHEMBL_ACT_16475227
PARP18.04IC509.22nMCHEMBL_ACT_29065399
PARP27.96IC5010.92nMCHEMBL_ACT_29065401
PARP27.82IC5015.3nMCHEMBL_ACT_17967445
PARP27.82IC5015.3nMCHEMBL_ACT_25998867
PARP27.81IC5015.49nMCHEMBL_ACT_17967375
PARP17.79IC5016.22nMCHEMBL_ACT_17967327
PARP17.78IC5016.7nMCHEMBL_ACT_17967464
PARP17.78IC5016.7nMCHEMBL_ACT_25616294

Target pathways

Aggregated over 2 target gene(s): PARP1, PARP2.

Top Reactome pathways

8 total, by targets touching each:

PathwayTargetsGenes
POLB-Dependent Long Patch Base Excision Repair2PARP1, PARP2
HDR through MMEJ (alt-NHEJ)2PARP1, PARP2
DNA Damage Recognition in GG-NER2PARP1, PARP2
Formation of Incision Complex in GG-NER2PARP1, PARP2
Dual Incision in GG-NER2PARP1, PARP2
vRNA Synthesis1PARP1
Downregulation of SMAD2/3:SMAD4 transcriptional activity1PARP1
SUMOylation of DNA damage response and repair proteins1PARP1

Dominant GO biological processes

GO termTargets
DNA repair2
double-strand break repair2
DNA damage response2
DNA ADP-ribosylation2
decidualization2
protein poly-ADP-ribosylation2
protein auto-ADP-ribosylation2
protein localization to chromatin2
DNA repair-dependent chromatin remodeling2
negative regulation of transcription by RNA polymerase II1
telomere maintenance1
transcription by RNA polymerase II1
apoptotic process1
mitochondrion organization1
transforming growth factor beta receptor signaling pathway1

Indications & clinical

Indications

43 indications (2 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).

IndicationTrial phaseMONDOEFO
neoplasm4MONDO:0005070EFO:0000616
ovarian carcinoma3MONDO:0005140EFO:0001075
hereditary breast ovarian cancer syndrome3MONDO:0003582Orphanet:145
small cell lung carcinoma3MONDO:0008433EFO:0000702
breast neoplasm3MONDO:0021100EFO:0003869
ovarian neoplasm3MONDO:0021068EFO:0003893
ovarian cancer3MONDO:0008170MONDO:0008170
non-small cell lung carcinoma3MONDO:0005233EFO:0003060
biliary tract neoplasm3MONDO:0005304EFO:0003891
HER2 positive breast carcinoma3MONDO:0006244EFO:1000294
prostate adenocarcinoma2MONDO:0005082EFO:0000673
lymphoma2MONDO:0005062EFO:0000574
metastatic prostate carcinoma2MONDO:0004956EFO:0000196
squamous cell carcinoma2MONDO:0005096EFO:0000707
metastatic melanoma2MONDO:0005191EFO:0002617
exocrine pancreatic carcinoma2MONDO:0005192EFO:0002618
urothelial carcinoma2MONDO:0040679EFO:0008528
endometrial carcinoma2MONDO:0002447EFO:1001512
colorectal adenocarcinoma2MONDO:0005008EFO:0000365
glioblastoma2MONDO:0018177EFO:0000519
cervical carcinoma2MONDO:0005131EFO:0001061
head and neck cancer2MONDO:0005627EFO:0006859
endometrium neoplasm2MONDO:0021251MONDO:0011962
head and neck squamous cell carcinoma2MONDO:0010150EFO:0000181
mesothelioma2MONDO:0005065EFO:0000588
prostate carcinoma2MONDO:0005159EFO:0001663
penile carcinoma2MONDO:0006360EFO:1000465
pancreatic ductal adenocarcinoma2MONDO:0005184MONDO:0005184
Ewing sarcoma1MONDO:0012817EFO:0000174
B-cell chronic lymphocytic leukemia1MONDO:0004948EFO:0000095
gastric neoplasm1MONDO:0021085MONDO:0001056
peritoneal neoplasm1MONDO:0006901MONDO:0002087
fallopian tube neoplasm1MONDO:0021092MONDO:0002158
lung neoplasm1MONDO:0021117MONDO:0008903
rectal cancer1MONDO:0006519EFO:1000657
paraganglioma1MONDO:0000448EFO:1000453

7 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 188.

Phase distribution

PhaseTrials
PHASE292
PHASE138
PHASE1/PHASE220
PHASE317
Not specified11
PHASE44
EARLY_PHASE14
PHASE2/PHASE32

Top trials by phase / activity

NCTPhaseStatusTitle
NCT06412120PHASE4RECRUITINGStudy Evaluating Safety, Tolerability, and Metabolism of Niraparib
NCT06887933PHASE4NOT_YET_RECRUITINGA Trial to Evaluate the Safety of Niraparib Tablets in Adult Female Participants With Advanced or Relapsed Epithelial Ovarian Cancer
NCT03752216PHASE4COMPLETEDNIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib.
NCT05187208PHASE4UNKNOWNPARP Inhibitor Oral Maintenance in Low-Risk Ovarian Cancer
NCT02655016PHASE3ACTIVE_NOT_RECRUITINGA Study of Niraparib (GSK3985771) Maintenance Treatment in Participants With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy
NCT03602859PHASE3ACTIVE_NOT_RECRUITINGA Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care (SOC) Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer
NCT03651206PHASE2/PHASE3RECRUITINGRecurrent Ovarian CarcinoSarcoma Anti-pd-1 Niraparib
NCT03748641PHASE3ACTIVE_NOT_RECRUITINGA Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Participants With Metastatic Prostate Cancer
NCT03768063PHASE3ACTIVE_NOT_RECRUITINGA Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study
NCT03981796PHASE3ACTIVE_NOT_RECRUITINGA Study to Evaluate Dostarlimab Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Participants With Recurrent or Primary Advanced Endometrial Cancer
NCT04497844PHASE3ACTIVE_NOT_RECRUITINGA Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC)
NCT04915755PHASE3ACTIVE_NOT_RECRUITINGEfficacy and Safety Comparison of Niraparib to Placebo in Participants With Human Epidermal Growth Factor 2 Negative (HER2-) Breast Cancer Susceptibility Gene Mutation (BRCAmut) or Triple-Negative Breast Cancer (TNBC) With Molecular Disease
NCT05009082PHASE3RECRUITINGNiraparib vs Niraparib Plus Bevacizumab in Patients With Platinum/Taxane-based Chemotherapy in Advanced Ovarian Cancer
NCT05615818PHASE3RECRUITINGPersonalized Medicine for Advanced Biliary Cancer Patients
NCT06388733PHASE3RECRUITINGA Study Comparing Niraparib With Temozolomide in Adult Participants With Newly-diagnosed, MGMT Unmethylated Glioblastoma
NCT06915025PHASE3RECRUITINGPhase 3 Trial Evaluating the Safety & Efficacy of IMNN-001 Administered in Combination w/ Standard NACT & Adjuvant Chemotherapy in Newly Diagnosed Patients w/ Advanced EOC, Fallopian Tube or Primary Peritoneal Cancer
NCT01905592PHASE3TERMINATEDA Phase III Trial of Niraparib Versus Physician’s Choice in HER2 Negative, Germline BRCA Mutation-positive Breast Cancer Patients
NCT03598270PHASE3COMPLETEDPlatinum-based Chemotherapy With Atezolizumab and Niraparib in Patients With Recurrent Ovarian Cancer
NCT03709316PHASE3UNKNOWNA Study of ZL-2306 (Niraparib) as Maintenance Treatment Following First-line Chemotherapy in Patients With Advanced Ovarian Cancer
NCT03806049PHASE3WITHDRAWNTrial Comparing Niraparib-bevacizumab-Dostarlimab and Niraparib-bevacizumab to Standard of Care in Recurrent Ovarian Cancer
NCT04159155PHASE2/PHASE3TERMINATEDA Study of Various Treatments in Serous or p53 Abnormal Endometrial Cancer
NCT04475939PHASE3COMPLETEDPlacebo-controlled Study Comparing Niraparib Plus Pembrolizumab Versus Placebo Plus Pembrolizumab as Maintenance Therapy in Participants With Advanced/Metastatic Non-Small Cell Lung Cancer
NCT04679064PHASE3UNKNOWNTrial on NIraparib-TSR-042 (Dostarlimab) vs Physician’s Choice CHEmotherapy in Recurrent, Ovarian, Fallopian Tube or Primary Peritoneal Cancer Patients Not Candidate for Platinum Retreatment
NCT01042379PHASE2RECRUITINGI-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer
NCT02925234PHASE2RECRUITINGThe Drug Rediscovery Protocol (DRUP Trial)
NCT03368729PHASE1/PHASE2ACTIVE_NOT_RECRUITINGNiraparib in Combination With Trastuzumab in Metastatic HER2+ Breast Cancer
NCT03431350PHASE2ACTIVE_NOT_RECRUITINGA Study of Niraparib Combination Therapies for the Treatment of Metastatic Castration-Resistant Prostate Cancer
NCT03830918PHASE1/PHASE2ACTIVE_NOT_RECRUITINGNiraparib, Temozolomide and Atezolizumab in Treating Patients With Advanced Solid Tumors and Extensive-Stage Small Cell Lung Cancer With a Complete or Partial Response to Platinum-Based First-Line Chemotherapy
NCT03983226PHASE2RECRUITINGSurgery and Niraparib in Secondary Recurrent Ovarian Cancer (SOC-3 Trial)
NCT03983993PHASE2ACTIVE_NOT_RECRUITINGNiraparib and Panitumumab in Patients With Advanced or Metastatic Colorectal Cancer
NCT04068753PHASE2ACTIVE_NOT_RECRUITINGNiraparib in Combination With Dostarlimab in Patients With Recurrent or Progressive Cervix Cancer
NCT04185831PHASE2ACTIVE_NOT_RECRUITINGA MolEcularly Guided Anti-Cancer Drug Off-Label Trial
NCT04194554PHASE1/PHASE2ACTIVE_NOT_RECRUITINGA Multi-Center Trial of Androgen Suppression With Abiraterone Acetate, Leuprolide, PARP Inhibition and Stereotactic Body Radiotherapy in Prostate Cancer
NCT04221503PHASE2ACTIVE_NOT_RECRUITINGNiraparib/TTFields in GBM
NCT04341181PHASE2RECRUITINGProTarget - A Danish Nationwide Clinical Trial on Targeted Cancer Treatment Based on Genomic Profiling
NCT04423185PHASE2RECRUITINGPLATFORM Study of Precision Medicine for Rare Tumors
NCT04507841PHASE2ACTIVE_NOT_RECRUITINGNiraparib for the Neoadjuvant Treatment of Unresectable Ovarian Cancer
NCT04584255PHASE2ACTIVE_NOT_RECRUITINGNiraparib + Dostarlimab In BRCA Mutated Breast Cancer
NCT04592237PHASE2ACTIVE_NOT_RECRUITINGCabazitaxel, Carboplatin, and Cetrelimab Followed by Niraparib With or Without Cetrelimab for the Treatment of Aggressive Variant Metastatic Prostate Cancer
NCT04641247PHASE2RECRUITINGA Long-term Treatment Extension Study of Niraparib in Participants Who Completed a Prior GlaxoSmithKline/TESARO-sponsored Niraparib Study

Clinical evidence (CIViC)

Variant × indication × effect (9 predictive associations from 9 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
BRCA1 Mutation OR BRCA2 MutationEpithelial Ovarian CancerSensitivity/ResponseNiraparibCIViC AEID11243
BRCA1 Mutation OR BRCA2 MutationPeritoneal CarcinomaSensitivity/ResponseNiraparibCIViC AEID11304
BRCA1 Mutation OR BRCA2 MutationFallopian Tube CarcinomaSensitivity/ResponseNiraparibCIViC AEID11305
BRCA1 Mutation OR BRCA2 MutationCastration-resistant Prostate CarcinomaSensitivity/ResponseAbiraterone + NiraparibCIViC AEID11738
BAP1 Q267fsClear Cell Renal Cell CarcinomaSensitivity/ResponseNiraparibCIViC CEID11199
MYCN OverexpressionNeuroblastomaSensitivity/ResponseNiraparib + Veliparib + Olaparib + TalazoparibCIViC DEID9006
PBRM1 Loss-of-functionBiliary Tract CancerSensitivity/ResponseNiraparibCIViC DEID12697
RB1 Loss-of-functionOsteosarcomaSensitivity/ResponseOlaparib + Niraparib + TalazoparibCIViC DEID12032
SLFN11 EXPRESSIONEwing SarcomaSensitivity/ResponseNiraparib + TemozolomideCIViC DEID5884

Pharmacology

Pharmacogenomics

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

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.

54 molecules share ≥1 primary target. Top 54 by shared-target count:

MoleculeSourceStatusShared targets
TALAZOPARIBChEMBL + PubChemPhase 4 (approved)PARP1, PARP2
OLAPARIBChEMBLPhase 4 (approved)PARP1, PARP2
RUCAPARIBChEMBLPhase 4 (approved)PARP1, PARP2
PAMIPARIBChEMBLPhase 3PARP1, PARP2
SARUPARIBChEMBLPhase 3PARP1, PARP2
VELIPARIBChEMBLPhase 3PARP1, PARP2
2X-121ChEMBLPhase 2PARP1, PARP2
AMITRIPTYLINEChEMBLPhase 4 (approved)PARP1
PALBOCICLIBChEMBLPhase 4 (approved)PARP1
RUCAPARIB CAMSYLATEChEMBLPhase 4 (approved)PARP1
FLUZOPARIBChEMBLPhase 3PARP1
INIPARIBChEMBLPhase 3PARP1
AMELPARIBChEMBLPhase 2PARP1
CHLORTHENOXAZINEChEMBLPhase 2PARP1
E-7016ChEMBLPhase 2PARP1
FLAVONEChEMBLPhase 2PARP1
LUTEOLINChEMBLPhase 2PARP1
NESUPARIBChEMBLPhase 2PARP1
AfatinibPubChemApprovedPARP1
ApixabanPubChemApprovedPARP1
belumosudilPubChemApprovedPARP1
BinimetinibPubChemApprovedPARP1
CarfilzomibPubChemApprovedPARP1
chenodiolPubChemApprovedPARP1
ClascoteronePubChemApprovedPARP1
ClofarabinePubChemApprovedPARP1
CrizotinibPubChemApprovedPARP1
cytisiniclinePubChemApprovedPARP1
dacomitinibPubChemApprovedPARP1
ElagolixPubChemApprovedPARP1
EribulinPubChemApprovedPARP1
FingolimodPubChemApprovedPARP1
IdelalisibPubChemApprovedPARP1
LactulosePubChemApprovedPARP1
LinagliptinPubChemApprovedPARP1
MavacamtenPubChemApprovedPARP1
MegestrolPubChemApprovedPARP1
NitisinonePubChemApprovedPARP1
PazopanibPubChemApprovedPARP1
podofiloxPubChemApprovedPARP1
PramipexolePubChemApprovedPARP1
PyrazinamidePubChemApprovedPARP1
regorafenibPubChemApprovedPARP1
RelugolixPubChemApprovedPARP1
RiociguatPubChemApprovedPARP1
RitlecitinibPubChemApprovedPARP1
RolapitantPubChemApprovedPARP1
saxagliptinPubChemApprovedPARP1
SelumetinibPubChemApprovedPARP1
TadalafilPubChemApprovedPARP1
TaurinePubChemApprovedPARP1
TrabectedinPubChemApprovedPARP1
TrametinibPubChemApprovedPARP1
VorapaxarPubChemApprovedPARP1

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
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Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot