olaparib indications/contra

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

Drug dosage:

None

Approvals:

DateAgencyCompanyOrphan
Oct. 23, 2014 EMA
Dec. 19, 2014 FDA ASTRAZENECA PHARMS

FDA Adverse Event Reporting System

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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 219.72 46.60 61 759 17732 3367307
Anaemia 174.23 46.60 67 753 54266 3330773
Off label use 112.36 46.60 49 771 53928 3331111
Nausea 104.97 46.60 62 758 129583 3255456
Acute myeloid leukaemia 102.95 46.60 26 794 5147 3379892
Myelodysplastic syndrome 91.01 46.60 24 796 5623 3379416
Disease progression 86.00 46.60 35 785 32224 3352815
Pneumonitis 84.09 46.60 23 797 6180 3378859
Carbohydrate antigen 125 increased 75.36 46.60 12 808 219 3384820
Vomiting 67.30 46.60 41 779 89490 3295549
Fatigue 62.93 46.60 42 778 107198 3277841
Thrombocytopenia 57.16 46.60 27 793 35241 3349798
Bone marrow failure 55.83 46.60 18 802 8469 3376570
Product use issue 51.71 46.60 20 800 15981 3369058

Pharmacologic Action:

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SourceCodeDescription
ATC L01XX46 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Other antineoplastic agents
FDA EPC N0000191623 Poly(ADP-Ribose) Polymerase Inhibitor
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D000067856 Poly(ADP-ribose) Polymerase Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent

Drug Use (View source of the data)

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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

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Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.54 acidic

Orange Book patent data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
50MG LYNPARZA ASTRAZENECA PHARMS N206162 Dec. 19, 2014 RX CAPSULE ORAL 8912187 March 12, 2024 TREATMENT OF BRCA MUTATED OVARIAN CANCER USING PARP INHIBITOR
100MG LYNPARZA ASTRAZENECA PHARMS N208558 Aug. 17, 2017 RX TABLET ORAL 8912187 March 12, 2024 MAINTENANCE TREATMENT OF RECURRENT EPITHELIAL OVARIAN, FALLOPIAN TUBE OR PRIMARY PERITONEAL CANCER, WHO ARE IN A COMPLETE OR PARTIAL RESPONSE TO PLATINUM-BASED CHEMOTHERAPY
100MG LYNPARZA ASTRAZENECA PHARMS N208558 Aug. 17, 2017 RX TABLET ORAL 8912187 March 12, 2024 TREATMENT OF DELETERIOUS OR SUSPECTED DELETERIOUS GERMLINE BRCA-MUTATED ADVANCED OVARIAN CANCER WHO HAVE BEEN TREATED WITH THREE OR MORE PRIOR LINES OF CHEMOTHERAPY BASED ON AN FDA-APPROVED COMPANION DIAGNOSTIC FOR LYNPARZA
150MG LYNPARZA ASTRAZENECA PHARMS N208558 Aug. 17, 2017 RX TABLET ORAL 8912187 March 12, 2024 MAINTENANCE TREATMENT OF RECURRENT EPITHELIAL OVARIAN, FALLOPIAN TUBE OR PRIMARY PERITONEAL CANCER, WHO ARE IN A COMPLETE OR PARTIAL RESPONSE TO PLATINUM-BASED CHEMOTHERAPY
150MG LYNPARZA ASTRAZENECA PHARMS N208558 Aug. 17, 2017 RX TABLET ORAL 8912187 March 12, 2024 TREATMENT OF DELETERIOUS OR SUSPECTED DELETERIOUS GERMLINE BRCA-MUTATED ADVANCED OVARIAN CANCER WHO HAVE BEEN TREATED WITH THREE OR MORE PRIOR LINES OF CHEMOTHERAPY BASED ON AN FDA-APPROVED COMPANION DIAGNOSTIC FOR LYNPARZA
50MG LYNPARZA ASTRAZENECA PHARMS N206162 Dec. 19, 2014 RX CAPSULE ORAL 8143241 Aug. 12, 2027 TREATMENT OF BRCA MUTATED OVARIAN CANCER USING PARP INHIBITOR
100MG LYNPARZA ASTRAZENECA PHARMS N208558 Aug. 17, 2017 RX TABLET ORAL 8143241 Aug. 12, 2027 MAINTENANCE TREATMENT OF BRCA-MUTATED RECURRENT EPITHELIAL OVARIAN, FALLOPIAN TUBE OR PRIMARY PERITONEAL CANCER, WHO ARE IN A COMPLETE OR PARTIAL RESPONSE TO PLATINUM-BASED CHEMOTHERAPY
100MG LYNPARZA ASTRAZENECA PHARMS N208558 Aug. 17, 2017 RX TABLET ORAL 8143241 Aug. 12, 2027 MAINTENANCE TREATMENT OF RECURRENT EPITHELIAL OVARIAN, FALLOPIAN TUBE OR PRIMARY PERITONEAL CANCER, WHO ARE IN A COMPLETE OR PARTIAL RESPONSE TO PLATINUM-BASED CHEMOTHERAPY
100MG LYNPARZA ASTRAZENECA PHARMS N208558 Aug. 17, 2017 RX TABLET ORAL 8143241 Aug. 12, 2027 TREATMENT OF DELETERIOUS OR SUSPECTED DELETERIOUS GERMLINE BRCA-MUTATED ADVANCED OVARIAN CANCER WHO HAVE BEEN TREATED WITH THREE OR MORE PRIOR LINES OF CHEMOTHERAPY BASED ON AN FDA-APPROVED COMPANION DIAGNOSTIC FOR LYNPARZA
150MG LYNPARZA ASTRAZENECA PHARMS N208558 Aug. 17, 2017 RX TABLET ORAL 8143241 Aug. 12, 2027 MAINTENANCE TREATMENT OF BRCA-MUTATED RECURRENT EPITHELIAL OVARIAN, FALLOPIAN TUBE OR PRIMARY PERITONEAL CANCER, WHO ARE IN A COMPLETE OR PARTIAL RESPONSE TO PLATINUM-BASED CHEMOTHERAPY
150MG LYNPARZA ASTRAZENECA PHARMS N208558 Aug. 17, 2017 RX TABLET ORAL 8143241 Aug. 12, 2027 MAINTENANCE TREATMENT OF RECURRENT EPITHELIAL OVARIAN, FALLOPIAN TUBE OR PRIMARY PERITONEAL CANCER, WHO ARE IN A COMPLETE OR PARTIAL RESPONSE TO PLATINUM-BASED CHEMOTHERAPY
150MG LYNPARZA ASTRAZENECA PHARMS N208558 Aug. 17, 2017 RX TABLET ORAL 8143241 Aug. 12, 2027 TREATMENT OF DELETERIOUS OR SUSPECTED DELETERIOUS GERMLINE BRCA-MUTATED ADVANCED OVARIAN CANCER WHO HAVE BEEN TREATED WITH THREE OR MORE PRIOR LINES OF CHEMOTHERAPY BASED ON AN FDA-APPROVED COMPANION DIAGNOSTIC FOR LYNPARZA
50MG LYNPARZA ASTRAZENECA PHARMS N206162 Dec. 19, 2014 RX CAPSULE ORAL 8859562 Aug. 4, 2031 TREATMENT OF BRCA MUTATED OVARIAN CANCER USING PARP INHIBITOR
100MG LYNPARZA ASTRAZENECA PHARMS N208558 Aug. 17, 2017 RX TABLET ORAL 8859562 Aug. 4, 2031 MAINTENANCE TREATMENT OF RECURRENT EPITHELIAL OVARIAN, FALLOPIAN TUBE OR PRIMARY PERITONEAL CANCER, WHO ARE IN A COMPLETE OR PARTIAL RESPONSE TO PLATINUM-BASED CHEMOTHERAPY
100MG LYNPARZA ASTRAZENECA PHARMS N208558 Aug. 17, 2017 RX TABLET ORAL 8859562 Aug. 4, 2031 TREATMENT OF DELETERIOUS OR SUSPECTED DELETERIOUS GERMLINE BRCA-MUTATED ADVANCED OVARIAN CANCER WHO HAVE BEEN TREATED WITH THREE OR MORE PRIOR LINES OF CHEMOTHERAPY BASED ON AN FDA-APPROVED COMPANION DIAGNOSTIC FOR LYNPARZA
150MG LYNPARZA ASTRAZENECA PHARMS N208558 Aug. 17, 2017 RX TABLET ORAL 8859562 Aug. 4, 2031 MAINTENANCE TREATMENT OF RECURRENT EPITHELIAL OVARIAN, FALLOPIAN TUBE OR PRIMARY PERITONEAL CANCER, WHO ARE IN A COMPLETE OR PARTIAL RESPONSE TO PLATINUM-BASED CHEMOTHERAPY
150MG LYNPARZA ASTRAZENECA PHARMS N208558 Aug. 17, 2017 RX TABLET ORAL 8859562 Aug. 4, 2031 TREATMENT OF DELETERIOUS OR SUSPECTED DELETERIOUS GERMLINE BRCA-MUTATED ADVANCED OVARIAN CANCER WHO HAVE BEEN TREATED WITH THREE OR MORE PRIOR LINES OF CHEMOTHERAPY BASED ON AN FDA-APPROVED COMPANION DIAGNOSTIC FOR LYNPARZA

Orange Book exclusivity data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
50MG LYNPARZA ASTRAZENECA PHARMS N206162 Dec. 19, 2014 RX CAPSULE ORAL Dec. 19, 2019 NEW CHEMICAL ENTITY
100MG LYNPARZA ASTRAZENECA PHARMS N208558 Aug. 17, 2017 RX TABLET ORAL Dec. 19, 2019 NEW CHEMICAL ENTITY
150MG LYNPARZA ASTRAZENECA PHARMS N208558 Aug. 17, 2017 RX TABLET ORAL Dec. 19, 2019 NEW CHEMICAL ENTITY
100MG LYNPARZA ASTRAZENECA PHARMS N208558 Aug. 17, 2017 RX TABLET ORAL Aug. 17, 2020 NEW PRODUCT
150MG LYNPARZA ASTRAZENECA PHARMS N208558 Aug. 17, 2017 RX TABLET ORAL Aug. 17, 2020 NEW PRODUCT
100MG LYNPARZA ASTRAZENECA PHARMS 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 PHARMS 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 PHARMS N206162 Dec. 19, 2014 RX 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 PHARMS 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 PHARMS 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

Bioactivity Summary:

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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:

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IDSource
7519 IUPHAR_LIGAND_ID
D09730 KEGG_DRUG
4034034 VUID
N0000191291 NUI
C2316164 UMLSCUI
CHEMBL521686 ChEMBL_ID
DB09074 DRUGBANK_ID
WOH1JD9AR8 UNII
8685 INN_ID
C531550 MESH_SUPPLEMENTAL_RECORD_UI
432162002 SNOMEDCT_US
432885003 SNOMEDCT_US
015824 NDDF
4034034 VANDF
30771 MMSL
d08319 MMSL
N0000191291 NDFRT
1597582 RXNORM
23725625 PUBCHEM_CID
CHEBI:83766 CHEBI
09L PDB_CHEM_ID

Pharmaceutical products:

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ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
Lynparza HUMAN PRESCRIPTION DRUG LABEL 1 0310-0657 CAPSULE 50 mg ORAL NDA 18 sections
Lynparza HUMAN PRESCRIPTION DRUG LABEL 1 0310-0668 TABLET, FILM COATED 100 mg ORAL NDA 18 sections
Lynparza HUMAN PRESCRIPTION DRUG LABEL 1 0310-0679 TABLET, FILM COATED 150 mg ORAL NDA 18 sections