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

Stem definitionDrug idCAS RN
poly-ADP-ribose polymerase inhibitors 5203 283173-50-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • rucaparib
  • rucaparib camsylate
  • AG-14447
  • rucaparib phosphate
  • AG-14699
  • AG014699
  • PF01367338
  • PF-1367338-BW
  • CO-338
  • rubraca
  • rucaparib camphorsulfonate
Rucaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP-1, PARP-2, and PARP-3, which play a role in DNA repair. In vitro studies have shown that rucaparib-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 rucaparib-induced cytotoxicity was observed in tumor cell lines with deficiencies in BRCA1/2 and other DNA repair genes. Rucaparib has been shown to decrease tumor growth in mouse xenograft models of human cancer with or without deficiencies in BRCA.
  • Molecular weight: 323.37
  • Formula: C19H18FN3O
  • CLOGP: 3.01
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 3
  • TPSA: 56.92
  • ALOGS: -4.45
  • ROTB: 3

  • Status: ONP

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

Drug dosage:

None

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 3.28 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 4.31 mL/min/kg Lombardo F, Berellini G, Obach RS
t_half (Half-life) 16.60 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
May 24, 2018 EMA Clovis Oncology UK Limited
Dec. 19, 2016 FDA Clovis Oncology, 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
Malignant neoplasm progression 1518.72 38.10 679 19634 64247 46601502
Carbohydrate antigen 125 increased 1445.64 38.10 308 20005 2102 46663647
Fatigue 1399.44 38.10 1497 18816 607200 46058549
Nausea 1126.13 38.10 1422 18891 686032 45979717
Dysgeusia 857.72 38.10 396 19917 40095 46625654
Product dose omission issue 728.73 38.10 594 19719 167926 46497823
Tumour marker increased 525.12 38.10 147 20166 3394 46662355
Adverse event 500.25 38.10 260 20053 33924 46631825
Taste disorder 484.31 38.10 155 20158 5723 46660026
Decreased appetite 420.25 38.10 467 19846 193369 46472380
Constipation 406.07 38.10 436 19877 173661 46492088
Underdose 381.62 38.10 181 20132 19377 46646372
Platelet count decreased 314.64 38.10 295 20018 99729 46566020
Accidental underdose 297.58 38.10 66 20247 552 46665197
Prescribed underdose 267.50 38.10 122 20191 11931 46653818
Blood count abnormal 258.45 38.10 135 20178 17743 46648006
Ovarian cancer recurrent 225.66 38.10 58 20255 953 46664796
Photosensitivity reaction 197.54 38.10 101 20212 12691 46653058
Red blood cell count decreased 183.63 38.10 135 20178 32488 46633261
Renal function test abnormal 164.72 38.10 57 20256 2682 46663067
Sunburn 157.77 38.10 54 20259 2458 46663291
Therapy partial responder 135.01 38.10 57 20256 4625 46661124
Vomiting 130.53 38.10 462 19851 452332 46213417
Asthenia 123.86 38.10 355 19958 310720 46355029
Liver function test increased 122.90 38.10 92 20221 22734 46643015
Blood creatinine increased 120.35 38.10 157 20156 76246 46589503
Anaemia 113.70 38.10 304 20009 255475 46410274
Abdominal pain upper 110.72 38.10 214 20099 145091 46520658
Drug ineffective 107.81 38.10 83 20230 677755 45987994
Haemoglobin decreased 100.77 38.10 192 20121 128757 46536992
Blood magnesium decreased 94.10 38.10 59 20254 10933 46654816
White blood cell count decreased 92.51 38.10 171 20142 112060 46553689
Abdominal distension 87.57 38.10 132 20181 73219 46592530
Drug hypersensitivity 86.07 38.10 5 20308 243820 46421929
Laboratory test abnormal 84.59 38.10 74 20239 22773 46642976
Abdominal discomfort 84.21 38.10 196 20117 150969 46514780
Abdominal pain 73.14 38.10 243 20070 229788 46435961
Flatulence 71.66 38.10 75 20238 28803 46636946
Intentional underdose 64.53 38.10 26 20287 1872 46663877
Dyspepsia 62.33 38.10 109 20204 68363 46597386
Pneumonia 60.96 38.10 45 20268 376275 46289474
Diarrhoea 59.49 38.10 431 19882 559171 46106578
Neuropathy peripheral 57.43 38.10 124 20189 90769 46574980
Early satiety 53.76 38.10 18 20295 765 46664984
Fall 52.44 38.10 40 20273 329057 46336692
Hepatic enzyme increased 45.41 38.10 106 20207 81681 46584068
Hypotension 40.01 38.10 26 20287 232563 46433186

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
Product use in unapproved indication 43.53 41.52 19 289 73674 29878496

Pharmacologic Action:

SourceCodeDescription
ATC L01XK03 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
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:62913 poly(adp-ribose) polymerase inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Malignant tumor of ovary indication 363443007 DOID:2394

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.08 acidic
pKa2 13.73 acidic
pKa3 9.45 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 200MG BASE RUBRACA CLOVIS ONCOLOGY INC N209115 Dec. 19, 2016 RX TABLET ORAL April 6, 2021 FOR THE 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 250MG BASE RUBRACA CLOVIS ONCOLOGY INC N209115 May 1, 2017 RX TABLET ORAL April 6, 2021 FOR THE 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 300MG BASE RUBRACA CLOVIS ONCOLOGY INC N209115 Dec. 19, 2016 RX TABLET ORAL April 6, 2021 FOR THE 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 200MG BASE RUBRACA CLOVIS ONCOLOGY INC N209115 Dec. 19, 2016 RX TABLET ORAL Dec. 19, 2021 NEW CHEMICAL ENTITY
EQ 250MG BASE RUBRACA CLOVIS ONCOLOGY INC N209115 May 1, 2017 RX TABLET ORAL Dec. 19, 2021 NEW CHEMICAL ENTITY
EQ 300MG BASE RUBRACA CLOVIS ONCOLOGY INC N209115 Dec. 19, 2016 RX TABLET ORAL Dec. 19, 2021 NEW CHEMICAL ENTITY
EQ 200MG BASE RUBRACA CLOVIS ONCOLOGY INC N209115 Dec. 19, 2016 RX TABLET ORAL May 15, 2023 TREATMENT OF ADULT PATIENTS WITH A DELETERIOUS BRCA MUTATION (GERMLINE AND/OR SOMATIC)-ASSOCIATED METASTATIC CASTRATION-RESISTANT PROSTATE CANCER WHO HAVE BEEN TREATED WITH ANDROGEN RECEPTOR-DIRECTED THERAPY AND A TAXANE-BASED CHEMOTHERAPY
EQ 250MG BASE RUBRACA CLOVIS ONCOLOGY INC N209115 May 1, 2017 RX TABLET ORAL May 15, 2023 TREATMENT OF ADULT PATIENTS WITH A DELETERIOUS BRCA MUTATION (GERMLINE AND/OR SOMATIC)-ASSOCIATED METASTATIC CASTRATION-RESISTANT PROSTATE CANCER WHO HAVE BEEN TREATED WITH ANDROGEN RECEPTOR-DIRECTED THERAPY AND A TAXANE-BASED CHEMOTHERAPY
EQ 300MG BASE RUBRACA CLOVIS ONCOLOGY INC N209115 Dec. 19, 2016 RX TABLET ORAL May 15, 2023 TREATMENT OF ADULT PATIENTS WITH A DELETERIOUS BRCA MUTATION (GERMLINE AND/OR SOMATIC)-ASSOCIATED METASTATIC CASTRATION-RESISTANT PROSTATE CANCER WHO HAVE BEEN TREATED WITH ANDROGEN RECEPTOR-DIRECTED THERAPY AND A TAXANE-BASED CHEMOTHERAPY
EQ 200MG BASE RUBRACA CLOVIS ONCOLOGY INC N209115 Dec. 19, 2016 RX TABLET ORAL Dec. 19, 2023 AS MONOTHERAPY FOR THE TREATMENT OF PATIENTS WITH DELETERIOUS BRCA MUTATION (GERMLINE AND/OR SOMATIC) ASSOCIATED ADVANCED OVARIAN CANCER WHO HAVE BEEN TREATED WITH TWO OR MORE CHEMOTHERAPIES
EQ 250MG BASE RUBRACA CLOVIS ONCOLOGY INC N209115 May 1, 2017 RX TABLET ORAL Dec. 19, 2023 AS MONOTHERAPY FOR THE TREATMENT OF PATIENTS WITH DELETERIOUS BRCA MUTATION (GERMLINE AND/OR SOMATIC) ASSOCIATED ADVANCED OVARIAN CANCER WHO HAVE BEEN TREATED WITH TWO OR MORE CHEMOTHERAPIES
EQ 300MG BASE RUBRACA CLOVIS ONCOLOGY INC N209115 Dec. 19, 2016 RX TABLET ORAL Dec. 19, 2023 AS MONOTHERAPY FOR THE TREATMENT OF PATIENTS WITH DELETERIOUS BRCA MUTATION (GERMLINE AND/OR SOMATIC) ASSOCIATED ADVANCED OVARIAN CANCER WHO HAVE BEEN TREATED WITH TWO OR MORE CHEMOTHERAPIES
EQ 200MG BASE RUBRACA CLOVIS ONCOLOGY INC N209115 Dec. 19, 2016 RX TABLET ORAL April 6, 2025 FOR THE 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 250MG BASE RUBRACA CLOVIS ONCOLOGY INC N209115 May 1, 2017 RX TABLET ORAL April 6, 2025 FOR THE 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 300MG BASE RUBRACA CLOVIS ONCOLOGY INC N209115 Dec. 19, 2016 RX TABLET ORAL April 6, 2025 FOR THE 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

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Poly [ADP-ribose] polymerase 1 Enzyme INHIBITOR IC50 8.50 SCIENTIFIC LITERATURE DRUG LABEL
Poly [ADP-ribose] polymerase 2 Enzyme INHIBITOR IC50 7.55 SCIENTIFIC LITERATURE DRUG LABEL
Poly [ADP-ribose] polymerase 3 Enzyme INHIBITOR IC50 6.39 SCIENTIFIC LITERATURE DRUG LABEL
Poly [ADP-ribose] polymerase 4 Enzyme INHIBITOR IC50 6.08 SCIENTIFIC LITERATURE
Tankyrase-1 Enzyme INHIBITOR IC50 6.84 SCIENTIFIC LITERATURE
Tankyrase-2 Enzyme INHIBITOR IC50 6.05 SCIENTIFIC LITERATURE
Poly [ADP-ribose] polymerase 10 Enzyme INHIBITOR IC50 6.25 SCIENTIFIC LITERATURE
Poly [ADP-ribose] polymerase 12 Enzyme INHIBITOR IC50 5.18 SCIENTIFIC LITERATURE
Poly [ADP-ribose] polymerase 14 Enzyme INHIBITOR IC50 5.05 SCIENTIFIC LITERATURE
Poly [ADP-ribose] polymerase 15 Enzyme INHIBITOR IC50 4.49 SCIENTIFIC LITERATURE

External reference:

IDSource
1859053-21-6 SECONDARY_CAS_RN
4036311 VANDF
C2603422 UMLSCUI
CHEBI:134689 CHEBI
RPB PDB_CHEM_ID
CHEMBL1173055 ChEMBL_ID
CHEMBL2105733 ChEMBL_ID
9931954 PUBCHEM_CID
CHEMBL3833368 ChEMBL_ID
D10079 KEGG_DRUG
7736 IUPHAR_LIGAND_ID
C531549 MESH_SUPPLEMENTAL_RECORD_UI
9471 INN_ID
DB12332 DRUGBANK_ID
8237F3U7EH UNII
1862578 RXNORM
247942 MMSL
32185 MMSL
d08507 MMSL
017056 NDDF
017057 NDDF
723984009 SNOMEDCT_US
763539004 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Rubraca HUMAN PRESCRIPTION DRUG LABEL 1 69660-201 TABLET, FILM COATED 200 mg ORAL NDA 28 sections
Rubraca HUMAN PRESCRIPTION DRUG LABEL 1 69660-202 TABLET, FILM COATED 250 mg ORAL NDA 28 sections
Rubraca HUMAN PRESCRIPTION DRUG LABEL 1 69660-203 TABLET, FILM COATED 300 mg ORAL NDA 28 sections