Identification

Summary

Olaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor used to treat ovarian cancer, breast cancer, pancreatic cancer, and prostate cancer.

Brand Names
Lynparza
Generic Name
Olaparib
DrugBank Accession Number
DB09074
Background

Olaparib is a selective and potent inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, PARP1 and PARP2.8,9 PARP inhibitors represent a novel class of anti-cancer therapy and they work by taking advantage of a defect in DNA repair in cancer cells with BRCA mutations and inducing cell death.4

Olaparib is used to treat a number of BRCA-associated tumours, including ovarian cancer, breast cancer, pancreatic cancer, and prostate cancer.8,9 It was first approved by the FDA and EU in December 2014,5 and by Health Canada in April 2016.12

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 434.4628
Monoisotopic: 434.175418827
Chemical Formula
C24H23FN4O3
Synonyms
  • 4-(3-{[4-(cyclopropylcarbonyl)piperazin-1-yl]carbonyl}-4-fluorobenzyl)phthalazin-1(2H)-one
  • Olaparib
External IDs
  • AZD 2281
  • AZD-2281
  • AZD2281
  • KU-0059436
  • KU-59436
  • KU59436

Pharmacology

Indication

Ovarian cancer

Olaparib is indicated for the maintenance treatment of adults with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy.8,11

Olaparib is indicated in combination with bevacizumab for the maintenance treatment of adults with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD)-positive status defined by either: a deleterious or suspected deleterious BRCA mutation, and/or genomic instability.8,11

Olaparib is indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy.8,11

Olaparib is indicated for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy.8,9

Breast cancer

Olaparib is indicated for the adjuvant treatment of adult patients with deleterious or suspected deleterious gBRCAm human epidermal growth factor receptor 2 (HER2)-negative high risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy.8,11,12

Olaparib is indicated for the treatment of adult patients with deleterious or suspected deleterious gBRCAm, HER2-negative metastatic breast cancer, who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR) positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy.8,11

Pancreatic cancer

Olaparib is indicated for the maintenance 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.8,11

Prostate cancer

Olaparib is indicated for the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with a hormone agent,11 such as enzalutamide or abiraterone.8

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Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

Olaparib is a cytotoxic and anti-tumour agent. Olaparib inhibits the growth of selective tumour cell lines in vitro and decreases tumour growth in mouse xenograft models of human cancer, both as monotherapy or following platinum-based chemotherapy. The drug exerts anti-tumour effects in cell lines and mouse tumour models with deficiencies in BRCA1/2, ATM, or other genes involved in the homologous recombination repair (HRR) of DNA damage and correlated with platinum response.8

In preclinical models of cancer, olaparib demonstrated anti-tumour activity when used alone, in combination with chemotherapeutic agents, or radiotherapy.5 Olaparib can act as a chemosensitizer to potentiate the cytotoxicity of DNA-damaging chemotherapeutic agents such as alkylating agents and platinum-based drugs. It can also act as a radiosensitizer by preventing PARP-mediated DNA repair.2,4

Mechanism of action

Poly(ADP-ribose) polymerases (PARPs) are multifunctional enzymes comprising 17 members. They are involved in normal cellular functions, such as DNA transcription and DNA repair.8 PARPs recognize and repair cellular DNA damage, such as single-strand breaks (SSBs) and double-strand breaks (DSBs). Different DNA repair pathways exist to repair these DNA damages, including the base excision repair (BER) pathway for SSBs and BRCA-dependent homologous recombination for DSBs.2

Olaparib is a PARP inhibitor: while it acts on PARP1, PARP2, and PARP3, olaparib is a more selective competitive inhibitor of NAD+ at the catalytic site of PARP1 and PARP2. Inhibition of the BER pathway by olaparib leads to the accumulation of unrepaired SSBs, which leads to the formation of DSBs, which is the most toxic form of DNA damage. While BRCA-dependent homologous recombination can repair DSBs in normal cells, this repair pathway is defective in cells with BRCA1/2 mutations, such as certain tumour cells.4 Inhibition of PARP in cancer cells with BRCA mutations leads to genomic instability and apoptotic cell death. This end result is also referred to as synthetic lethality, a phenomenon where the combination of two defects - inhibition of PARP activity and loss of DSB repair by HR - that are otherwise benign when alone, lead to detrimental results.2

In vitro studies have shown that olaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes, resulting in DNA damage and cancer cell death.8

TargetActionsOrganism
APoly [ADP-ribose] polymerase 1
inhibitor
Humans
APoly [ADP-ribose] polymerase 2
inhibitor
Humans
APoly [ADP-ribose] polymerase 3
inhibitor
Humans
UAldo-keto reductase family 1 member C3
inhibitor
Humans
Absorption

Following oral administration, olaparib is rapidly absorbed.1 After administration of a single 300 mg dose of olaparib, the mean (CV%) Cmax was 5.4 μg/mL (32%) and AUC was 39.2 μg x h/mL (44%). The steady state Cmax and AUC following a dose of 300 mg twice daily was 7.6 μg/mL (35%) and 49.2 μg x h/mL (44%), respectively. Tmax is 1.5 hours. A high-fat and high-calorie meal may delay Tmax, but does not significantly alter the extent of olaparib absorption.8

Volume of distribution

The mean (± standard deviation) apparent volume of distribution of olaparib is 158 ± 136 L following a single 300 mg dose.8

Protein binding

The protein binding of olaparib is approximately 82% in vitro.8 In solutions of purified proteins, the olaparib fraction bound to albumin was approximately 56% and the fraction bound to alpha-1 acid glycoprotein was 29%.7

Metabolism

Olaparib is metabolized by cytochrome P450 (CYP) 3A4/5 in vitro. Following an oral dose of radiolabeled olaparib to female patients, unchanged olaparib accounted for 70% of the circulating radioactivity in plasma. Olaparib undergoes oxidation reactions as well as subsequent glucuronide or sulfate conjugation.8 In humans, olaparib can also undergo hydrolysis, hydroxylation, and dehydrogenation.3

While up to 37 metabolites of olaparib were detected in plasma, urine, and feces, the majority of metabolites represent less than 1% of the total administered dose and they have not been fully characterized. The major circulating metabolites are a ring-opened piperazin-3-ol moiety and two mono-oxygenated metabolites. The pharmacodynamic activity of the metabolites is unknown.7

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Route of elimination

Following a single dose of radiolabeled olaparib, 86% of the dosed radioactivity was recovered within a seven-day collection period, mostly in the form of metabolites. About 44% of the drug was excreted via the urine and 42% of the dose was excreted via the feces. Following an oral dose of radiolabeled olaparib to female patients, the unchanged drug accounted for 15% and 6% of the radioactivity in urine and feces, respectively.8

Half-life

Following a single oral dose in patients with cancer, the mean terminal half-life was 6.10 hours.6

Clearance

Following a single oral dose in patients with cancer, the mean apparent plasma clearance was 4.55 L/h.6

Adverse Effects
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Toxicity

The oral LD50 in rats is approximately 240-300 mg/kg.10

There is limited information regarding the overdose of olaparib.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Olaparib can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Olaparib can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Olaparib.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Olaparib.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Olaparib.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Olaparib.
AcetaminophenThe metabolism of Olaparib can be increased when combined with Acetaminophen.
AcetazolamideThe metabolism of Olaparib can be decreased when combined with Acetazolamide.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Olaparib.
AdalimumabThe metabolism of Olaparib can be increased when combined with Adalimumab.
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Food Interactions
  • Avoid grapefruit products. Grapefruit inhibits the CYP3A metabolism of olaparib, which may increase its serum concentration.
  • Avoid St. John's Wort. This herb induces the CYP3A metabolism of olaparib and may reduce its serum concentration.
  • Take with or without food. Food does not significantly alter the extent of olaparib absorption.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
LynparzaCapsule50 mg/1OralAstraZeneca Pharmaceuticals LP2014-12-242020-03-31US flag
LynparzaTablet, film coated100 mgOralAstra Zeneca Ab2021-02-10Not applicableEU flag
LynparzaTablet150 mgOralAstra Zeneca2018-05-23Not applicableCanada flag
LynparzaTablet, film coated150 mg/1OralAstraZeneca Pharmaceuticals LP2017-08-17Not applicableUS flag
LynparzaTablet, film coated150 mgOralAstra Zeneca Ab2021-02-10Not applicableEU flag
LynparzaTablet, film coated100 mgOralAstra Zeneca Ab2021-02-10Not applicableEU flag
LynparzaTablet100 mgOralAstra Zeneca2018-05-23Not applicableCanada flag
LynparzaTablet, film coated100 mg/1OralAstraZeneca Pharmaceuticals LP2017-08-17Not applicableUS flag
LynparzaTablet, film coated150 mgOralAstra Zeneca Ab2021-02-10Not applicableEU flag
LynparzaCapsule50 mgOralAstra Zeneca Ab2021-02-10Not applicableEU flag

Categories

ATC Codes
L01XK01 — Olaparib
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phthalazinones. These are compounds containing a phthalazine bearing a ketone group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazanaphthalenes
Sub Class
Benzodiazines
Direct Parent
Phthalazinones
Alternative Parents
2-halobenzoic acids and derivatives / Benzamides / Benzoyl derivatives / Fluorobenzenes / Pyridazines and derivatives / Piperazines / Aryl fluorides / Cyclopropanecarboxylic acids and derivatives / Vinylogous halides / Tertiary carboxylic acid amides
show 8 more
Substituents
1,4-diazinane / 2-halobenzoic acid or derivatives / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Benzamide / Benzenoid / Benzoic acid or derivatives / Benzoyl
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
cyclopropanes, monofluorobenzenes, phthalazines, N-acylpiperazine (CHEBI:83766)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
WOH1JD9AR8
CAS number
763113-22-0
InChI Key
FDLYAMZZIXQODN-UHFFFAOYSA-N
InChI
InChI=1S/C24H23FN4O3/c25-20-8-5-15(14-21-17-3-1-2-4-18(17)22(30)27-26-21)13-19(20)24(32)29-11-9-28(10-12-29)23(31)16-6-7-16/h1-5,8,13,16H,6-7,9-12,14H2,(H,27,30)
IUPAC Name
4-{[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorophenyl]methyl}-1,2-dihydrophthalazin-1-one
SMILES
FC1=CC=C(CC2=NNC(=O)C3=CC=CC=C23)C=C1C(=O)N1CCN(CC1)C(=O)C1CC1

References

Synthesis Reference

Menear KA, Adcock C, Boulter R, Cockcroft XL, Copsey L, Cranston A, Dillon KJ, Drzewiecki J, Garman S, Gomez S, Javaid H, Kerrigan F, Knights C, Lau A, Loh VM Jr, Matthews IT, Moore S, O'Connor MJ, Smith GC, Martin NM: 4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin- 1-one: a novel bioavailable inhibitor of poly(ADP-ribose) polymerase-1. J Med Chem. 2008 Oct 23;51(20):6581-91. doi: 10.1021/jm8001263. Epub 2008 Sep 19. Pubmed

General References
  1. Solimando DA Jr, Waddell JA: Nivolumab and Olaparib. Hosp Pharm. 2015 May;50(5):356-66. doi: 10.1310/hpj5005-356. [Article]
  2. Bochum S, Berger S, Martens UM: Olaparib. Recent Results Cancer Res. 2018;211:217-233. doi: 10.1007/978-3-319-91442-8_15. [Article]
  3. Wang L, Wang M: In vitro metabolism of olaparib in liver microsomes by liquid chromatography/electrospray ionization high-resolution mass spectrometry. Rapid Commun Mass Spectrom. 2020 Feb 15;34(3):e8575. doi: 10.1002/rcm.8575. [Article]
  4. Sachdev E, Tabatabai R, Roy V, Rimel BJ, Mita MM: PARP Inhibition in Cancer: An Update on Clinical Development. Target Oncol. 2019 Dec;14(6):657-679. doi: 10.1007/s11523-019-00680-2. [Article]
  5. Deeks ED: Olaparib: first global approval. Drugs. 2015 Feb;75(2):231-40. doi: 10.1007/s40265-015-0345-6. [Article]
  6. Chen Y, Zhang L, Hao Q: Olaparib: a promising PARP inhibitor in ovarian cancer therapy. Arch Gynecol Obstet. 2013 Aug;288(2):367-74. doi: 10.1007/s00404-013-2856-2. Epub 2013 Apr 26. [Article]
  7. New Zealand Data Sheet: LYNPARZA (olaparib) Oral Capsules [Link]
  8. FDA Approved Drug Products: LYNPARZA (olaparib) tablets, for oral use [Link]
  9. FDA Approved Drug Products: LYNPARZA (olaparib) capsules, for oral use [Link]
  10. Astrazeneca: Lynparza (Olaparib) MSDS [Link]
  11. EMA Approved Drug Products: Lynparza (olaparib) Oral Tablets [Link]
  12. Health Canada Approved Drug Products: LYNPARZA (Olaparib) Oral Tablets [Link]
Human Metabolome Database
HMDB0255929
KEGG Drug
D09730
ChemSpider
23343272
BindingDB
27566
RxNav
1597582
ChEBI
83766
ChEMBL
CHEMBL521686
ZINC
ZINC000040430143
PDBe Ligand
09L
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Olaparib
PDB Entries
3u9y / 4tkg / 4tvj / 5ds3 / 7aad / 7kk4 / 7kko

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentBreast Cancer / Ovarian Cancer1
4CompletedOtherBRCA or HRR+ Mutated Ovarian Cancer Patients1
4RecruitingTreatmentCancer1
4RecruitingTreatmentMetastatic Castration Resistant Prostate Cancer (CRPC)1
3Active Not RecruitingTreatmentAbdominal wall neoplasm / Fallopian Tubes Cancer / Ovarian Cancer1
3Active Not RecruitingTreatmentAdvanced Ovarian Cancer / BRCA Mutations / Complete Response / FIGO Stage III-IV / First Line Platinum Chemotherapy / Newly Diagnosed / Partial Response1
3Active Not RecruitingTreatmentBRCA 1 Gene Mutation / BRCA 2 Gene Mutation / Metastatic Breast Cancer1
3Active Not RecruitingTreatmentBRCA Mutated / Following Complete or Partial Response to Platinum Based Chemotherapy / Platinum Sensitive / Recurrent Ovarian Cancer1
3Active Not RecruitingTreatmentBreast Cancer1
3Active Not RecruitingTreatmentCarcinoma, Squamous Cell, Non-small-cell Lung1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral50 mg/1
TabletOral100 mg
TabletOral150 mg
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral100 Mg
Tablet, film coatedOral150 mg/1
Tablet, film coatedOral150 Mg
Tablet, coatedOral100 mg
Tablet, coatedOral150 mg
Tablet, film coatedOral
CapsuleOral50 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8859562No2014-10-142031-08-04US flag
US8912187No2014-12-162024-03-12US flag
US8143241No2012-03-272027-08-12US flag
US7449464No2008-11-112024-10-11US flag
US8247416No2012-08-212028-09-24US flag
US7151102No2006-12-192022-04-29US flag
US7981889No2011-07-192024-10-11US flag
US8071579No2011-12-062027-08-12US flag
US8475842No2013-07-022029-12-31US flag
US9566276No2017-02-142024-03-12US flag
US9169235No2015-10-272024-03-12US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)198https://www.fishersci.com/store/msds?partNumber=AC466292500&productDescription=OLAPARIB+250MG&vendorId=VN00032119&countryCode=US&language=en
Predicted Properties
PropertyValueSource
Water Solubility0.0601 mg/mLALOGPS
logP2.72ALOGPS
logP1.96ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)9.96ChemAxon
pKa (Strongest Basic)-0.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area82.08 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity117.53 m3·mol-1ChemAxon
Polarizability43.81 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
Olaparib inhibits PARP1 with an IC50 of 5 nM.
General Function
Zinc ion binding
Specific Function
Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This ...
Gene Name
PARP1
Uniprot ID
P09874
Uniprot Name
Poly [ADP-ribose] polymerase 1
Molecular Weight
113082.945 Da
References
  1. Verhagen CV, de Haan R, Hageman F, Oostendorp TP, Carli AL, O'Connor MJ, Jonkers J, Verheij M, van den Brekel MW, Vens C: Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells. Radiother Oncol. 2015 Sep;116(3):358-65. doi: 10.1016/j.radonc.2015.03.028. Epub 2015 May 13. [Article]
  2. Tavares TS, Hofman J, Lekesova A, Zelazkova J, Wsol V: Olaparib Synergizes the Anticancer Activity of Daunorubicin via Interaction with AKR1C3. Cancers (Basel). 2020 Oct 26;12(11). pii: cancers12113127. doi: 10.3390/cancers12113127. [Article]
  3. Bochum S, Berger S, Martens UM: Olaparib. Recent Results Cancer Res. 2018;211:217-233. doi: 10.1007/978-3-319-91442-8_15. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
Olaparib inhibits PARP1 with an IC50 of 1 nM.
General Function
Nad+ adp-ribosyltransferase activity
Specific Function
Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This ...
Gene Name
PARP2
Uniprot ID
Q9UGN5
Uniprot Name
Poly [ADP-ribose] polymerase 2
Molecular Weight
66205.31 Da
References
  1. Verhagen CV, de Haan R, Hageman F, Oostendorp TP, Carli AL, O'Connor MJ, Jonkers J, Verheij M, van den Brekel MW, Vens C: Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells. Radiother Oncol. 2015 Sep;116(3):358-65. doi: 10.1016/j.radonc.2015.03.028. Epub 2015 May 13. [Article]
  2. Bochum S, Berger S, Martens UM: Olaparib. Recent Results Cancer Res. 2018;211:217-233. doi: 10.1007/978-3-319-91442-8_15. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Nad+ adp-ribosyltransferase activity
Specific Function
Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This ...
Gene Name
PARP3
Uniprot ID
Q9Y6F1
Uniprot Name
Poly [ADP-ribose] polymerase 3
Molecular Weight
60069.7 Da
References
  1. Verhagen CV, de Haan R, Hageman F, Oostendorp TP, Carli AL, O'Connor MJ, Jonkers J, Verheij M, van den Brekel MW, Vens C: Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells. Radiother Oncol. 2015 Sep;116(3):358-65. doi: 10.1016/j.radonc.2015.03.028. Epub 2015 May 13. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
Specific Function
Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2....
Gene Name
AKR1C3
Uniprot ID
P42330
Uniprot Name
Aldo-keto reductase family 1 member C3
Molecular Weight
36852.89 Da
References
  1. Tavares TS, Hofman J, Lekesova A, Zelazkova J, Wsol V: Olaparib Synergizes the Anticancer Activity of Daunorubicin via Interaction with AKR1C3. Cancers (Basel). 2020 Oct 26;12(11). pii: cancers12113127. doi: 10.3390/cancers12113127. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
In vitro, olaparib (17-500 μM) inhibited CYP3A4/5 with an IC50 of 119 μM.
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Verhagen CV, de Haan R, Hageman F, Oostendorp TP, Carli AL, O'Connor MJ, Jonkers J, Verheij M, van den Brekel MW, Vens C: Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells. Radiother Oncol. 2015 Sep;116(3):358-65. doi: 10.1016/j.radonc.2015.03.028. Epub 2015 May 13. [Article]
  2. McCormick A, Swaisland H, Reddy VP, Learoyd M, Scarfe G: In vitro evaluation of the inhibition and induction potential of olaparib, a potent poly(ADP-ribose) polymerase inhibitor, on cytochrome P450. Xenobiotica. 2018 Jun;48(6):555-564. doi: 10.1080/00498254.2017.1346332. Epub 2017 Jul 25. [Article]
  3. Bochum S, Berger S, Martens UM: Olaparib. Recent Results Cancer Res. 2018;211:217-233. doi: 10.1007/978-3-319-91442-8_15. [Article]
  4. FDA Approved Drug Products: LYNPARZA (olaparib) tablets, for oral use [Link]
  5. Linparza (olaparib) drug monograph [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
In vitro, olaparib (17-500 μM) inhibited CYP3A4/5 with an IC50 of 119 μM.
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. McCormick A, Swaisland H, Reddy VP, Learoyd M, Scarfe G: In vitro evaluation of the inhibition and induction potential of olaparib, a potent poly(ADP-ribose) polymerase inhibitor, on cytochrome P450. Xenobiotica. 2018 Jun;48(6):555-564. doi: 10.1080/00498254.2017.1346332. Epub 2017 Jul 25. [Article]
  2. FDA Approved Drug Products: LYNPARZA (olaparib) tablets, for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Verhagen CV, de Haan R, Hageman F, Oostendorp TP, Carli AL, O'Connor MJ, Jonkers J, Verheij M, van den Brekel MW, Vens C: Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells. Radiother Oncol. 2015 Sep;116(3):358-65. doi: 10.1016/j.radonc.2015.03.028. Epub 2015 May 13. [Article]
  2. Olaparib Health Canada Product Monograph [File]
  3. Olaparib EMA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. New Zealand Data Sheet: LYNPARZA (olaparib) Oral Capsules [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. New Zealand Data Sheet: LYNPARZA (olaparib) Oral Capsules [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. New Zealand Data Sheet: LYNPARZA (olaparib) Oral Capsules [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
Curator comments
This agent is a substrate and inhibitor of P-glycoprotein in vitro, but prescribing information states that this is unlikely to be of clinical significance.
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. New Zealand Data Sheet: LYNPARZA (olaparib) Oral Capsules [Link]
  2. FDA Approved Drug Products: LYNPARZA (olaparib) tablets, for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. New Zealand Data Sheet: LYNPARZA (olaparib) Oral Capsules [Link]

Drug created at May 14, 2015 20:38 / Updated at October 07, 2022 09:51