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Rucaparib

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Also known as AG-14447SID103905261SID137276017AG-014699SID174006354

Summary

Rucaparib (CHEMBL1173055) is an approved small-molecule EC 2.4.2.30 (NAD+ ADP-ribosyltransferase) inhibitor (ATC L01XK03) targeting PARP1; indicated across 19 conditions including neoplasm and peritoneal neoplasm; with CIViC clinical evidence for 18 variant-indication associations (e.g. BRCA1 Mutation in ovarian cancer).

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: L01XK03
  • Targets: 1 (PARP1)
  • Indications: 19 conditions
  • Clinical trials: 60
  • Precision-oncology evidence (CIViC): 18 variant–indication associations
  • Chemistry: 323.4 Da · C19H18FN3O

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL1173055
NameRucaparib
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID9931954
ChEBICHEBI:134689
ATCL01XK03
Molecular formulaC19H18FN3O
Molecular weight323.4
InChIKeyHMABYWSNWIZPAG-UHFFFAOYSA-N

SMILES: CNCC1=CC=C(C=C1)C2=C3CCNC(=O)C4=C3C(=CC(=C4)F)N2

IUPAC name: 6-fluoro-2-[4-(methylaminomethyl)phenyl]-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-9-one

ChEBI definition: A member of the class of azepinoindoles that is 1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one carrying additional 4-[(methylamino)methyl]phenyl and fluoro substituents at positions 2 and 8 respectively. It is an inhibitor of poly (ADP-ribose) polymerase and is used (as the camsylate salt) as monotherapy for advanced ovarian cancer and deleterious germline or somatic BRCA mutation.

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

Also known as: AG-14447, Rucaparib, SID103905261, RUCAPARIB, SID137276017, AG-014699, SID174006354, rucaparib

Parent form; salt/anhydrous children: CHEMBL2105733, CHEMBL3833368

Patent coverage: 2,988 distinct patent families (7,009 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 6,680 (95%) of the total. 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 1Inhibition8.854.1%P09874

Broader ChEMBL bioactivity targets: 29 (assay-derived). Sample: DNA polymerase alpha catalytic subunit, Progesterone receptor, Beta-1 adrenergic receptor, Serine/threonine-protein kinase pim-1, Protein mono-ADP-ribosyltransferase PARP14, Protein mono-ADP-ribosyltransferase PARP15, Sodium-dependent noradrenaline transporter, Alpha-1A adrenergic receptor, Dual specificity tyrosine-phosphorylation-regulated kinase 1A, Prostaglandin G/H synthase 2.

Bioactivity

ChEMBL activities: 98 potent at pChembl ≥ 5 of 108 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
PARP29.4IC500.4nMCHEMBL_ACT_24919330
POLA19.4IC500.4nMCHEMBL_ACT_25553945
PARP29.3IC500.5nMCHEMBL_ACT_18847945
PARP29.3IC500.5nMCHEMBL_ACT_24790244
PARP29.3IC500.5nMCHEMBL_ACT_24984885
PARP29.3IC500.5nMCHEMBL_ACT_25662126
PARP29.3IC500.5nMCHEMBL_ACT_25884152
PARP29.3IC500.5nMCHEMBL_ACT_25998868
PARP19.15IC500.7nMCHEMBL_ACT_22432611
PARP29.15Ki0.7nMCHEMBL_ACT_22432630
PARP19.1IC500.8nMCHEMBL_ACT_15721287
PARP19.1IC500.8nMCHEMBL_ACT_18847944
PARP29.1IC500.8nMCHEMBL_ACT_22432629
PARP19.1IC500.8nMCHEMBL_ACT_24790235
PARP19.1IC500.8nMCHEMBL_ACT_24919410
PARP19.1IC500.8nMCHEMBL_ACT_24984884
PARP19.1IC500.8nMCHEMBL_ACT_25662118
PARP19.1IC500.8nMCHEMBL_ACT_25884147
PARP19.1IC500.8nMCHEMBL_ACT_25998864
PARP18.85Ki1.4nMCHEMBL_ACT_13897704
PARP18.85Ki1.4nMCHEMBL_ACT_19441986
PARP18.85Ki1.4nMCHEMBL_ACT_19483634
PARP18.85Ki1.4nMCHEMBL_ACT_22432612
PARP18.85Ki1.4nMCHEMBL_ACT_24775558
PARP18.85Ki1.4nMCHEMBL_ACT_24993432
PARP18.85Ki1.4nMCHEMBL_ACT_25898553
PARP18.85IC501.4nMCHEMBL_ACT_29118511
PARP28.82IC501.5nMCHEMBL_ACT_24775565
PARP18.77IC501.7nMCHEMBL_ACT_24775560
PARP18.7IC501.98nMCHEMBL_ACT_16475225

Target pathways

Aggregated over 1 target gene(s): PARP1.

Top Reactome pathways

8 total, by targets touching each:

PathwayTargetsGenes
POLB-Dependent Long Patch Base Excision Repair1PARP1
vRNA Synthesis1PARP1
Downregulation of SMAD2/3:SMAD4 transcriptional activity1PARP1
SUMOylation of DNA damage response and repair proteins1PARP1
HDR through MMEJ (alt-NHEJ)1PARP1
DNA Damage Recognition in GG-NER1PARP1
Formation of Incision Complex in GG-NER1PARP1
Dual Incision in GG-NER1PARP1

Dominant GO biological processes

GO termTargets
negative regulation of transcription by RNA polymerase II1
telomere maintenance1
DNA repair1
double-strand break repair1
transcription by RNA polymerase II1
apoptotic process1
DNA damage response1
mitochondrion organization1
transforming growth factor beta receptor signaling pathway1
response to gamma radiation1
positive regulation of cardiac muscle hypertrophy1
carbohydrate biosynthetic process1
protein autoprocessing1
signal transduction involved in regulation of gene expression1
macrophage differentiation1

Indications & clinical

Indications

19 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
peritoneal neoplasm3MONDO:0006901MONDO:0002087
fallopian tube neoplasm3MONDO:0021092MONDO:0002158
ovarian cancer3MONDO:0008170MONDO:0008170
exocrine pancreatic carcinoma2MONDO:0005192EFO:0002618
hereditary breast ovarian cancer syndrome2MONDO:0003582Orphanet:145
mesothelioma2MONDO:0005065EFO:0000588
uterine carcinosarcoma2MONDO:0006485EFO:1000613
gastric neoplasm2MONDO:0021085MONDO:0001056
breast neoplasm2MONDO:0021100MONDO:0007254
endometrium neoplasm2MONDO:0021251MONDO:0011962
leiomyosarcoma2MONDO:0005058EFO:0000564
pancreatic ductal adenocarcinoma2MONDO:0005184MONDO:0005184
non-small cell lung carcinoma1MONDO:0005233EFO:0003060
small cell lung carcinoma1MONDO:0008433EFO:0000702

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

Clinical trials

Total trials: 60.

Phase distribution

PhaseTrials
PHASE230
PHASE1/PHASE211
PHASE19
PHASE37
Not specified2
EARLY_PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT03522246PHASE3ACTIVE_NOT_RECRUITINGA Study in Ovarian Cancer Patients Evaluating Rucaparib and Nivolumab as Maintenance Treatment Following Response to Front-Line Platinum-Based Chemotherapy
NCT03768063PHASE3ACTIVE_NOT_RECRUITINGA Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study
NCT01968213PHASE3COMPLETEDPhase 3 Study of Rucaparib as Switch Maintenance After Platinum in Relapsed High Grade Serous or Endometrioid Ovarian Cancer (ARIEL3)
NCT02855944PHASE3COMPLETEDARIEL4: A Study of Rucaparib Versus Chemotherapy BRCA Mutant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients
NCT02975934PHASE3COMPLETEDA Study of Rucaparib Versus Physician’s Choice of Therapy in Participants With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency
NCT04227522PHASE3COMPLETEDRucaparib MAintenance After Bevacizumab Maintenance Following Carboplatin Based First Line Chemotherapy in Ovarian Cancer Patients
NCT04676334PHASE3COMPLETEDCATCH-R: A Rollover Study to Provide Continued Access to Rucaparib
NCT02678182PHASE2ACTIVE_NOT_RECRUITINGPlanning Treatment for Oesophago-gastric Cancer: a Maintenance Therapy Trial
NCT02873962PHASE2ACTIVE_NOT_RECRUITINGA Phase II Study Of Nivolumab/ Bevacizumab/Rucaparib
NCT02925234PHASE2RECRUITINGThe Drug Rediscovery Protocol (DRUP Trial)
NCT03337087PHASE1/PHASE2ACTIVE_NOT_RECRUITINGLiposomal Irinotecan, Fluorouracil, Leucovorin Calcium, and Rucaparib in Treating Patients With Metastatic Pancreatic, Colorectal, Gastroesophageal, or Biliary Cancer
NCT03899155PHASE2RECRUITINGPan Tumor Rollover Study
NCT04253262PHASE1/PHASE2ACTIVE_NOT_RECRUITINGA Study of Copanlisib Combined With Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer
NCT04624178PHASE2ACTIVE_NOT_RECRUITINGA Study of Rucaparib and Nivolumab in People With Leiomyosarcoma
NCT00457470PHASE2WITHDRAWNA Phase 2 Study Exploring The Safety And Efficacy Of Novel Drug Treatment In Subjects With Diabetic Macular Edema (DME)
NCT00664781PHASE2COMPLETEDRucaparib(CO-338;Formally Called AG-014699 or PF-0136738) in Treating Patients With Locally Advanced or Metastatic Breast Cancer or Advanced Ovarian Cancer
NCT01074970PHASE2COMPLETEDPARP Inhibition for Triple Negative Breast Cancer (ER-/PR-/HER2-)With BRCA1/2 Mutations
NCT01482715PHASE1/PHASE2COMPLETEDA Study of Oral Rucaparib in Patients With a Solid Tumor (Phase I) or With gBRCA Mutation Ovarian Cancer (Phase II)
NCT01891344PHASE2COMPLETEDA Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2)
NCT02042378PHASE2COMPLETEDA Study of Rucaparib in Patients With Pancreatic Cancer and a Known Deleterious BRCA Mutation
NCT02505048PHASE2COMPLETEDA Study to Assess the Efficacy of Rucaparib in Metastatic Breast Cancer Patients With a BRCAness Genomic Signature
NCT02711137PHASE1/PHASE2TERMINATEDOpen-Label Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies
NCT02935634PHASE2COMPLETEDA Study to Test Combination Treatments in Participants With Advanced Gastric Cancer
NCT02952534PHASE2COMPLETEDA Study of Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency
NCT03140670PHASE2TERMINATEDMaintenance Rucaparib in BRCA1, BRCA2 or PALB2 Mutated Pancreatic Cancer That Has Not Progressed on Platinum-based Therapy
NCT03338790PHASE2COMPLETEDAn Investigational Immunotherapy Study of Nivolumab in Combination With Rucaparib, Docetaxel, or Enzalutamide in Metastatic Castration-resistant Prostate Cancer
NCT03397394PHASE2TERMINATEDRucaparib in Patients With Locally Advanced or Metastatic Urothelial Carcinoma
NCT03413995PHASE2COMPLETEDTrial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations
NCT03442556PHASE2TERMINATEDDocetaxel, Carboplatin, and Rucaparib Camsylate in Treating Patients With Metastatic Castration Resistant Prostate Cancer With Homologous Recombination DNA Repair Deficiency
NCT03462212PHASE1/PHASE2UNKNOWNCarboplatin-Paclitaxel-Bevacizumab vs Carbo-Pacli-Beva-Rucaparib vs Carbo-Pacli-Ruca, Selected According to HRD Status, in Patients With Advanced Ovarian, Primary Peritoneal and Fallopian Tube Cancer, Preceded by a Phase I Dose Escalation Study on Ruca-Beva Combination
NCT03476798PHASE2COMPLETEDBevacizumab and Rucaparib in Recurrent Carcinoma of the Cervix or Endometrium
NCT03533946PHASE2TERMINATEDRucaparib in Nonmetastatic prOstAte With BRCAness
NCT03559049PHASE1/PHASE2TERMINATEDRucaparib and Pembrolizumab for Maintenance Therapy in Stage IV Non-Squamous Non-Small Cell Lung Cancer
NCT03572478PHASE1/PHASE2TERMINATEDRucaparib and Nivolumab in Patients With Prostate or Endometrial Cancer
NCT03617679PHASE2COMPLETEDRucaparib vs Placebo Maintenance Therapy in Metastatic and Recurrent Endometrial Cancer
NCT03639935PHASE2COMPLETEDRucaparib in Combination With Nivolumab in Patients With Advanced or Metastatic Biliary Tract Cancer Following Platinum Therapy
NCT03654833PHASE2UNKNOWNMesothelioma Stratified Therapy (MiST) : A Multi-drug Phase II Trial in Malignant Mesothelioma
NCT03694262PHASE2COMPLETEDThe EndoBARR Trial (Endometrial Bevacizumab, Atezolizumab, Rucaparib)
NCT03795272PHASE2WITHDRAWNRucaparib Maintenance Therapy in Advanced Cervical Cancer
NCT03824704PHASE2TERMINATEDA Study to Evaluate Rucaparib in Combination With Nivolumab in Patients With Selected Solid Tumors (ARIES)

Clinical evidence (CIViC)

Variant × indication × effect (18 predictive associations from 28 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
BRCA1 MutationOvarian CancerSensitivity/ResponseRucaparibCIViC AEID11136 +3
BRCA2 MutationOvarian CancerSensitivity/ResponseRucaparibCIViC AEID11137 +3
BRCA1 Mutation OR BRCA2 MutationFallopian Tube, Ovarian Cancer, And Peritoneal Serous CarcinomaSensitivity/ResponseRucaparibCIViC AEID11246
BRCA1 Mutation OR BRCA2 MutationCastration-resistant Prostate CarcinomaSensitivity/ResponseRucaparibCIViC AEID12944
BRCA2 MutationPancreatic CancerSensitivity/ResponseRucaparibCIViC BEID7436 +3
BRCA1 MutationPancreatic CancerSensitivity/ResponseRucaparibCIViC BEID9291 +1
BRCA1 Loss-of-function OR BAP1 Loss-of-functionMalignant MesotheliomaSensitivity/ResponseRucaparibCIViC BEID11739
BRCA1 Mutation OR BRCA2 Mutation OR PALB2 MutationPancreatic AdenocarcinomaSensitivity/ResponseRucaparibCIViC BEID11317
PALB2 MutationBreast CancerSensitivity/ResponseRucaparibCIViC BEID7460
PALB2 MutationPancreatic CancerSensitivity/ResponseRucaparibCIViC BEID9294
BRCA1 Q1467*Ovarian CancerSensitivity/ResponseRucaparibCIViC CEID2878
BRCA2 M1IOvarian CancerSensitivity/ResponseRucaparibCIViC CEID2880
BRCA2 M1ROvarian CancerSensitivity/ResponseRucaparibCIViC CEID2879
BRCA2 R2336POvarian CancerSensitivity/ResponseRucaparibCIViC CEID2884
BRCA2 V159MOvarian CancerSensitivity/ResponseRucaparibCIViC CEID2881
BRCA2 V211IOvarian CancerSensitivity/ResponseRucaparibCIViC CEID2883
BRCA2 V211LOvarian CancerSensitivity/ResponseRucaparibCIViC CEID2882
CDK12 Loss-of-functionProstate CancerSensitivity/ResponseTalazoparib + Olaparib + Rucaparib + VeliparibCIViC DEID12572

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.

53 molecules share ≥1 primary target. Top 53 by shared-target count:

MoleculeSourceStatusShared targets
AMITRIPTYLINEChEMBLPhase 4 (approved)PARP1
NIRAPARIBChEMBLPhase 4 (approved)PARP1
OLAPARIBChEMBLPhase 4 (approved)PARP1
PALBOCICLIBChEMBLPhase 4 (approved)PARP1
TALAZOPARIBChEMBLPhase 4 (approved)PARP1
FLUZOPARIBChEMBLPhase 3PARP1
INIPARIBChEMBLPhase 3PARP1
PAMIPARIBChEMBLPhase 3PARP1
SARUPARIBChEMBLPhase 3PARP1
VELIPARIBChEMBLPhase 3PARP1
2X-121ChEMBLPhase 2PARP1
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