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

Stem definitionDrug idCAS RN
poly-ADP-ribose polymerase inhibitors 4907 763113-22-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • olaparib
  • lynparza
  • AZD2281
Olaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2, and PARP3. PARP enzymes are involved in normal cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNA repair. Olaparib has been shown to inhibit growth of select tumor cell lines in vitro and decrease tumor growth in mouse xenograft models of human cancer both as monotherapy or following platinum-based chemotherapy. Increased cytotoxicity and anti-tumor activity following treatment with olaparib were noted in cell lines and mouse tumor models with deficiencies in BRCA. In vitro studies have shown that olaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complex, resulting in disruption of cellular homeostasis and cell death.
  • Molecular weight: 434.47
  • Formula: C24H23FN4O3
  • CLOGP: 1.24
  • LIPINSKI: 0
  • HAC: 7
  • HDO: 1
  • TPSA: 82.08
  • ALOGS: -3.86
  • ROTB: 4

  • Status: ONP

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

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Hosey CM, Chan R, Benet LZ

Approvals:

DateAgencyCompanyOrphan
Jan. 19, 2018 PMDA AstraZeneca KK
Dec. 19, 2014 FDA ASTRAZENECA PHARMS
Oct. 23, 2014 EMA

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 1460.30 30.74 471 5468 64455 46615668
Anaemia 601.96 30.74 382 5557 255397 46424726
Acute myeloid leukaemia 500.96 30.74 150 5789 15628 46664495
Myelodysplastic syndrome 484.27 30.74 146 5793 15565 46664558
Carbohydrate antigen 125 increased 220.63 30.74 53 5886 2357 46677766
Ovarian cancer recurrent 201.40 30.74 42 5897 969 46679154
Death 164.82 30.74 207 5732 335341 46344782
Disease progression 118.98 30.74 96 5843 91204 46588919
Interstitial lung disease 118.88 30.74 78 5861 53871 46626252
Nausea 90.72 30.74 239 5700 687215 45992908
Neutrophil count decreased 86.50 30.74 59 5880 43367 46636756
Haematotoxicity 80.31 30.74 31 5908 6902 46673221
Pancytopenia 79.43 30.74 74 5865 84984 46595139
Bone marrow failure 78.00 30.74 48 5891 29621 46650502
Myelosuppression 77.14 30.74 31 5908 7672 46672451
Tumour marker increased 75.91 30.74 25 5914 3516 46676607
Platelet count decreased 72.89 30.74 76 5863 99948 46580175
Pneumonitis 69.71 30.74 44 5895 28376 46651747
Metastases to central nervous system 65.92 30.74 31 5908 11190 46668933
Metastases to liver 65.42 30.74 37 5902 19548 46660575
Ileus 65.06 30.74 33 5906 14031 46666092
Thrombocytopenia 63.09 30.74 79 5860 126502 46553621
Metastases to peritoneum 62.05 30.74 20 5919 2628 46677495
Renal impairment 51.45 30.74 55 5884 74317 46605806
Metastasis 48.93 30.74 19 5920 4293 46675830
BRCA2 gene mutation 47.01 30.74 8 5931 57 46680066
Musculoskeletal toxicity 43.66 30.74 6 5933 6 46680117
Intestinal obstruction 37.25 30.74 29 5910 26046 46654077
Off label use 37.00 30.74 119 5820 379722 46300401
Blood creatinine increased 36.91 30.74 47 5892 76356 46603767
Acute leukaemia 32.51 30.74 10 5929 1128 46678995
Disease recurrence 31.85 30.74 23 5916 18448 46661675

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
Off label use 139.71 56.33 73 466 249217 29702722
Death 122.89 56.33 76 463 357207 29594732
Product use in unapproved indication 92.11 56.33 38 501 73655 29878284
Malignant neoplasm progression 69.44 56.33 31 508 72256 29879683

Pharmacologic Action:

SourceCodeDescription
ATC L01XK01 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
CHEBI has role CHEBI:68495 type i programmed cell-death inducer

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Epithelial tumor of ovary indication 237057005 DOID:2152
Malignant tumor of ovary indication 363443007 DOID:2394
Malignant tumor of peritoneum indication 363492001

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.54 acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
100MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL Jan. 12, 2021 TREATMENT OF DELETERIOUS OR SUSPECTED DELETERIOUS GERMLINE BRCA-MUTATED, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2-NEGATIVE METASTATIC BREAST CANCER WHO HAVE BEEN TREATED WITH CHEMOTHERAPY IN THE NEOADJUVANT, ADJUVANT OR METASTATIC SETTING
150MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL Jan. 12, 2021 TREATMENT OF DELETERIOUS OR SUSPECTED DELETERIOUS GERMLINE BRCA-MUTATED, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2-NEGATIVE METASTATIC BREAST CANCER WHO HAVE BEEN TREATED WITH CHEMOTHERAPY IN THE NEOADJUVANT, ADJUVANT OR METASTATIC SETTING
50MG LYNPARZA ASTRAZENECA N206162 Dec. 19, 2014 DISCN CAPSULE ORAL Dec. 19, 2021 USE OF AS MONOTHERAPY FOR PATIENTS WITH DELETERIOUS OR SUSPECTED DELETERIOUS GERMLINE BRCA MUTATED (AS DETECTED BY AN FDA-APPROVED TEST) ADVANCED OVARIAN CANCER WHO HAVE BEEN TREATED WITH THREE OR MORE PRIOR LINES OF CHEMOTHERAPY
100MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL Dec. 19, 2021 FIRSTLINE MAINTENULLNCE TX IN PTS W/ DELETERIOUS OR SUSPECTED DELETERIOUS GERMLINE, SOMATIC BRCA-MUTATED ADVANCED EPITHELIAL OVARIAN, FALLOPIAN TUBE OR PRIMARY PERITONEAL CA WHO ARE IN COMPLETE OR PARTIAL RESPONSE TO FIRSTLINE PLATINUM-BASED CHEMOTHERAPY
100MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL Dec. 19, 2021 USE OF AS MONOTHERAPY FOR PATIENTS WITH DELETERIOUS OR SUSPECTED DELETERIOUS GERMLINE BRCA MUTATED (AS DETECTED BY AN FDA-APPROVED TEST) ADVANCED OVARIAN CANCER WHO HAVE BEEN TREATED WITH THREE OR MORE PRIOR LINES OF CHEMOTHERAPY
150MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL Dec. 19, 2021 FIRSTLINE MAINTENULLNCE TX IN PTS W/ DELETERIOUS OR SUSPECTED DELETERIOUS GERMLINE, SOMATIC BRCA-MUTATED ADVANCED EPITHELIAL OVARIAN, FALLOPIAN TUBE OR PRIMARY PERITONEAL CA WHO ARE IN COMPLETE OR PARTIAL RESPONSE TO FIRSTLINE PLATINUM-BASED CHEMOTHERAPY
150MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL Dec. 19, 2021 USE OF AS MONOTHERAPY FOR PATIENTS WITH DELETERIOUS OR SUSPECTED DELETERIOUS GERMLINE BRCA MUTATED (AS DETECTED BY AN FDA-APPROVED TEST) ADVANCED OVARIAN CANCER WHO HAVE BEEN TREATED WITH THREE OR MORE PRIOR LINES OF CHEMOTHERAPY
100MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL Dec. 27, 2022 MAINTENULLNCE TREATMENT OF ADULT PATIENTS WITH DELETERIOUS OR SUSPECTED DELETERIOUS GBRCAM METASTATIC PANCREATIC ADENOCARCINOMA WHOSE DISEASE HAS NOT PROGRESSED ON AT LEAST 16 WEEKS OF A FIRST-LINE PLATINUM-BASED CHEMOTHERAPY REGIMEN
150MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL Dec. 27, 2022 MAINTENULLNCE TREATMENT OF ADULT PATIENTS WITH DELETERIOUS OR SUSPECTED DELETERIOUS GBRCAM METASTATIC PANCREATIC ADENOCARCINOMA WHOSE DISEASE HAS NOT PROGRESSED ON AT LEAST 16 WEEKS OF A FIRST-LINE PLATINUM-BASED CHEMOTHERAPY REGIMEN
100MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL May 8, 2023 W/BEVACIZUMAB FOR MAINTENULLNCE TX OF ADULTS W/ADV. EPITHELIAL OVARIAN, FALLOPIAN TUBE OR PRIMARY PERITONEAL CA IN COMPLETE OR PARTIAL RESPONSE TO FIRST-LINE PLATINUM-BASED CHEMO & CA ASSOCIATED W/ HOMOLOGOUS RECOMBINULLTION DEFICIENCY POSITIVE STATUS
150MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL May 8, 2023 W/BEVACIZUMAB FOR MAINTENULLNCE TX OF ADULTS W/ADV. EPITHELIAL OVARIAN, FALLOPIAN TUBE OR PRIMARY PERITONEAL CA IN COMPLETE OR PARTIAL RESPONSE TO FIRST-LINE PLATINUM-BASED CHEMO & CA ASSOCIATED W/ HOMOLOGOUS RECOMBINULLTION DEFICIENCY POSITIVE STATUS
100MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL May 19, 2023 TX OF ADULT PTS WITH DELETERIOUS OR SUSPECTED DELETERIOUS GERMLINE OR SOMATIC HOMOLOGOUS RECOMBINULLTION REPAIR GENE-MUTATED METASTATIC CASTRATION-RESISTANT PROSTATE CANCER WHO HAVE PROGRESSED FOLLOWING PRIOR TREATMENT WITH ENZALUTAMIDE OR ABIRATERONE
150MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL May 19, 2023 TX OF ADULT PTS WITH DELETERIOUS OR SUSPECTED DELETERIOUS GERMLINE OR SOMATIC HOMOLOGOUS RECOMBINULLTION REPAIR GENE-MUTATED METASTATIC CASTRATION-RESISTANT PROSTATE CANCER WHO HAVE PROGRESSED FOLLOWING PRIOR TREATMENT WITH ENZALUTAMIDE OR ABIRATERONE
100MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL Aug. 17, 2024 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
100MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL Aug. 17, 2024 TREATMENT OF ADULT PATIENTS WITH DELETERIOUS OR SUSPECTED DELETERIOUS GERMLINE BRCA-MUTATED ADVANCED OVARIAN CANCER WHO HAVE BEEN TREATED WITH THREE OR MORE PRIOR LINES OF CHEMOTHERAPY
150MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL Aug. 17, 2024 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
150MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL Aug. 17, 2024 TREATMENT OF ADULT PATIENTS WITH DELETERIOUS OR SUSPECTED DELETERIOUS GERMLINE BRCA-MUTATED ADVANCED OVARIAN CANCER WHO HAVE BEEN TREATED WITH THREE OR MORE PRIOR LINES OF CHEMOTHERAPY
100MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL Dec. 19, 2025 MAINTENULLNCE TREATMENT OF ADULTS WITH DELETERIOUS OR SUSPECTED DELETERIOUS GERMLINE OR SOMATIC BRCA-MUTATED ADVANCED EPITHELIAL OVARIAN, FALLOPIAN TUBE, OR PRIMARY PERITONEAL CANCER IN COMPLETE OR PARTIAL RESPONSE TO FIRST-LINE PLATINUM-BASED CHEMOTHERAPY
150MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL Dec. 19, 2025 MAINTENULLNCE TREATMENT OF ADULTS WITH DELETERIOUS OR SUSPECTED DELETERIOUS GERMLINE OR SOMATIC BRCA-MUTATED ADVANCED EPITHELIAL OVARIAN, FALLOPIAN TUBE, OR PRIMARY PERITONEAL CANCER IN COMPLETE OR PARTIAL RESPONSE TO FIRST-LINE PLATINUM-BASED CHEMOTHERAPY
100MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL Dec. 27, 2026 MAINTENULLNCE TX OF ADULTS W/ DELETERIOUS OR SUSPECTED DELETERIOUS GBRCAM METASTATIC PANCREATIC ADENOCARCINOMA WHOSE DZ HAS NOT PROGRESSED ON >=16WKS OF 1ST LINE PLATINUM BASED CHEMO REGIMEN. SELECT PTS FOR THERAPY BASED ON APPROVED COMPANION DIAGNOSTIC
150MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL Dec. 27, 2026 MAINTENULLNCE TX OF ADULTS W/ DELETERIOUS OR SUSPECTED DELETERIOUS GBRCAM METASTATIC PANCREATIC ADENOCARCINOMA WHOSE DZ HAS NOT PROGRESSED ON >=16WKS OF 1ST LINE PLATINUM BASED CHEMO REGIMEN. SELECT PTS FOR THERAPY BASED ON APPROVED COMPANION DIAGNOSTIC
100MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL May 8, 2027 W/ BEVACIZUMAB FOR MAINT TX OF ADULTS W/ ADV EPITHELIAL OVARIAN, FALLOPIAN TUBE, OR PRIMARY PERITONEAL CA IN COMPLETE OR PARTIAL RESPONSE TO 1ST LINE PT BASED CHEMO & WHOSE CA IS ASSOC W/ HOMOLOGOUS RECOMB DEF + STATUS DEFINED BY GENOMIC INSTABILITY
150MG LYNPARZA ASTRAZENECA N208558 Aug. 17, 2017 RX TABLET ORAL May 8, 2027 W/ BEVACIZUMAB FOR MAINT TX OF ADULTS W/ ADV EPITHELIAL OVARIAN, FALLOPIAN TUBE, OR PRIMARY PERITONEAL CA IN COMPLETE OR PARTIAL RESPONSE TO 1ST LINE PT BASED CHEMO & WHOSE CA IS ASSOC W/ HOMOLOGOUS RECOMB DEF + STATUS DEFINED BY GENOMIC INSTABILITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Poly [ADP-ribose] polymerase 1 Enzyme INHIBITOR IC50 8.30 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Poly [ADP-ribose] polymerase 2 Enzyme INHIBITOR IC50 9 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Poly [ADP-ribose] polymerase 3 Enzyme INHIBITOR IC50 7.34 CHEMBL DRUG LABEL
Tankyrase-1 Enzyme IC50 5.82 SCIENTIFIC LITERATURE

External reference:

IDSource
D09730 KEGG_DRUG
4034034 VUID
N0000191291 NUI
4034034 VANDF
C2347419 UMLSCUI
CHEBI:83766 CHEBI
09L PDB_CHEM_ID
CHEMBL521686 ChEMBL_ID
23725625 PUBCHEM_CID
DB09074 DRUGBANK_ID
C531550 MESH_SUPPLEMENTAL_RECORD_UI
7519 IUPHAR_LIGAND_ID
8685 INN_ID
WOH1JD9AR8 UNII
1597582 RXNORM
231537 MMSL
30771 MMSL
d08319 MMSL
015824 NDDF
432162002 SNOMEDCT_US
432885003 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Lynparza HUMAN PRESCRIPTION DRUG LABEL 1 0310-0668 TABLET, FILM COATED 100 mg ORAL NDA 26 sections
Lynparza HUMAN PRESCRIPTION DRUG LABEL 1 0310-0679 TABLET, FILM COATED 150 mg ORAL NDA 26 sections