Identification

Name
Olaparib
Accession Number
DB09074
Description

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.

Olaparib is available as oral tablets marketed under the brand name Lynparza and was initially indicated as a maintenance therapy or monotherapy for the treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer. On January 12, 2018, FDA expanded the approved use of Lynparza to include chemotherapy-experienced patients with germline breast cancer susceptibility gene (BRCA) mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. In a randomized clinical trial involving patients with HER2-negative metastatic breast cancer with a germline BRCA mutation, the median progression-free survival for patients taking Lynparza was 7 months compared to 4.2 months for patients taking chemotherapy only. Patient selection for this newly-approved indication can be performed based on an FDA-approved genetic test, called the BRACAnalysis CDx.

Moreover, in December of 2018 the FDA further approved the categorization and use of Lynparza (olaparib) as frontline maintenance therapy in ovarian cancer, making the medication the first time a PARP inhibitor has been approved in the first-line maintenance setting 7. This new approval for frontline maintenance now allows patients who have had surgery and complete or partial response to platinum-based therapy after being first diagnosed with the cancer to be treated with olaparib to decrease the risk of recurrence or delay it significantly 7. This approval is based on findings from the phase 3 SOLO-1 trial for olaparib, which demonstrated the capacity for the agent to reduce the risk of disease progression or death by 70% in patients with BRCA-mutant advanced ovarian cancer who were in complete or partial response to platinum-based chemotherapy 7. It is expected that the ability to offer this important first-line maintenance treatment option to eligible patients may slow down or even stop the natural course of disease progression 7.

Type
Small Molecule
Groups
Approved
Structure
Thumb
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

Olaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for the treatment of:

(I) Ovarian cancer, in which the medication is intended for [a] 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, or [b] 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 Label. Select patients for therapy based on an FDA-approved companion diagnostic for olaparib Label.

[II] Breast cancer, in which the medication is intended for use in patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have previously 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 treatment Label. Select patients for therapy based on an FDA-approved companion diagnostic for olaparib Label.

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

The effect of olaparib on cardiac repolarization was assessed in 119 patients following a single dose of 300 mg and in 109 patients following multiple dosing of 300 mg twice daily Label. No clinically relevant effect of olaparib on QT interval was observed Label.

Mechanism of action

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 Label. 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 Label. Increased cytotoxicity and anti-tumor activity following treatment with olaparib were noted in cell lines and mouse tumor models with deficiencies in BRCA Label. 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 Label.

TargetActionsOrganism
APoly [ADP-ribose] polymerase 1
inhibitor
Humans
APoly [ADP-ribose] polymerase 2
inhibitor
Humans
APoly [ADP-ribose] polymerase 3
inhibitor
Humans
Absorption

Following oral administration, the absorption of olaparib is very rapid and can reach a peak concentration ranging between 4.7 and 9.1 mcg/ml after 1-3 hours. The reported AUC of olaparib after a dose of 200 mg is of 25.8 mcg.h/L and this AUC can be increased by 26% with constant administration. The consumption of a high-fat diet with olaparib can only decrease the tmax but do not have an effect in the peak concentration.6

Volume of distribution

After administration of a dose of 100 mg/kg, the reported volume of distribution was of 40.3 L.6

Protein binding

In vitro studies have reported that the plasma protein binding of olaparib was reported to be of 82%.5

Metabolism

Olaparib is extensively metabolized in the liver by the action of CYP3A isoenzymes.9 From the administered dose, the unchanged form of olaparib accounted for 70% of the circulating dose and it was considered the major component in urine and feces.8

The metabolic pathway of olaparib is mainly attributable to oxidation reactions with subsequent glucuronide and sulfate conjugation. However, the over 20 metabolites found in plasma, urine, and feces represented a minor portion of the administered dose. The major circulating metabolites were represented by the mono-oxygenated form and the piperazin-3-ol form.8

Route of elimination

From the administered dose, approximately 86% of the administered dose is recovered after 7 days from which 44% is found in the urine and 42% is obtained in feces.8

Half-life

The reported elimination half-life ranges between 5 to 11 hours.6

Clearance

The total clearance of olaparib was reported to be 4.6 L/h.6

Adverse Effects
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Toxicity

The most commonly reported side effects reported during clinical trials included cough, constipation, dysgeusia, peripheral deem, back pain, dizziness, headache, urinary tract infection, dyspnea, and rash Label 8,9. Myelodysplastic syndrome/Acute Myeloid Leukemia (MDS/AML) was reported in 2% of patients with deleterious or suspected deleterious germline BRCA-mutated advanced cancers Label 8,9. The majority of cases were fatal and the duration of therapy with olaparib in patients who developed secondary cancers varied from <6 months to >2 years Label 8,9. Complete blood count should be tested at baseline and monthly following therapy initiation to monitor for MDS/AML Label 8,9. Pneumonitis, including fatal cases, occurred in <1% of patients treated with olaparib Label 8,9. Patients should be monitored for new or worsening respiratory symptoms such as dyspnea, fever, cough, or wheezing Label 8,9. Olaparib was found to be teratogenic and causes embryo-fetal toxicity in rats Label 8,9. It should, therefore, be avoided during pregnancy and its use should be combined with effective contraception during treatment Label 8,9.

Affected organisms
  • Humans and other mammals
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 Olaparib can be decreased when combined with Acalabrutinib.
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.
Additional Data Available
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  • Evidence Level
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  • Action
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    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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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.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
LynparzaCapsule50 mgOralAstra Zeneca2016-05-16Not applicableCanada flag
LynparzaCapsule50 mg/1OralAstraZeneca Pharmaceuticals LP2014-12-242020-03-31US flag
LynparzaTablet150 mgOralAstra Zeneca2018-05-23Not applicableCanada flag
LynparzaTablet, film coated150 mg/1OralAstraZeneca Pharmaceuticals LP2017-08-17Not applicableUS flag
LynparzaTablet100 mgOralAstra Zeneca2018-05-23Not applicableCanada flag
LynparzaTablet, film coated100 mg/1OralAstraZeneca Pharmaceuticals LP2017-08-17Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
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    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
L01XX46 — 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)

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. Frampton JE: Olaparib: a review of its use as maintenance therapy in patients with ovarian cancer. BioDrugs. 2015 Apr;29(2):143-50. doi: 10.1007/s40259-015-0125-6. [PubMed:25899311]
  2. 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:18800822]
  3. Hay T, Matthews JR, Pietzka L, Lau A, Cranston A, Nygren AO, Douglas-Jones A, Smith GC, Martin NM, O'Connor M, Clarke AR: Poly(ADP-ribose) polymerase-1 inhibitor treatment regresses autochthonous Brca2/p53-mutant mammary tumors in vivo and delays tumor relapse in combination with carboplatin. Cancer Res. 2009 May 1;69(9):3850-5. doi: 10.1158/0008-5472.CAN-08-2388. Epub 2009 Apr 21. [PubMed:19383921]
  4. Rottenberg S, Jaspers JE, Kersbergen A, van der Burg E, Nygren AO, Zander SA, Derksen PW, de Bruin M, Zevenhoven J, Lau A, Boulter R, Cranston A, O'Connor MJ, Martin NM, Borst P, Jonkers J: High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs. Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):17079-84. doi: 10.1073/pnas.0806092105. Epub 2008 Oct 29. [PubMed:18971340]
  5. Irwin CP, Portorreal Y, Brand C, Zhang Y, Desai P, Salinas B, Weber WA, Reiner T: PARPi-FL--a fluorescent PARP1 inhibitor for glioblastoma imaging. Neoplasia. 2014 May;16(5):432-40. doi: 10.1016/j.neo.2014.05.005. Epub 2014 Jun 23. [PubMed:24970386]
  6. Solimando DA Jr, Waddell JA: Nivolumab and Olaparib. Hosp Pharm. 2015 May;50(5):356-66. doi: 10.1310/hpj5005-356. [PubMed:26405320]
  7. FDA Approves Olaparib as Frontline Maintenance Therapy in Ovarian Cancer Press Release [Link]
  8. Olaparib New Zealand Data Sheet [Link]
  9. Linparza (olaparib) drug monograph [File]
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
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
3u9y / 4tkg / 4tvj / 5ds3
FDA label
Download (481 KB)
MSDS
Download (109 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingOtherBRCA or HRR+ Mutated Ovarian Cancer Patients1
4RecruitingTreatmentBreast Cancer / Ovarian Cancer1
3Active Not RecruitingTreatmentAdvanced Ovarian Cancer / BRCA Mutation / 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 RecruitingTreatmentFallopian Tube Clear Cell Adenocarcinoma / Fallopian Tube Transitional Cell Carcinoma / Fallopian Tube Undifferentiated Carcinoma / Ovarian Clear Cell Adenocarcinoma / Ovarian Endometrioid Tumor / Ovarian Seromucinous Carcinoma / Ovarian Serous Tumor / Ovarian Transitional Cell Carcinoma / Ovarian Undifferentiated Carcinoma / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Ovarian Endometrioid Adenocarcinoma / Recurrent Primary Peritoneal Carcinoma1
3Active Not RecruitingTreatmentFollowing Complete or Partial Response to Platinum Based Chemotherapy / Platinum Sensitive / Recurrent Ovarian Cancer1
3Active Not RecruitingTreatmentGermline BRCA1/2 Mutations and / Metastatic Adenocarcinoma of the Pancreas1
3Active Not RecruitingTreatmentGermline BRCA1/2 Mutations / HER2-ve Metastatic Breast Cancer / Somatic BRCA1/2 Mutations1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral50 mg/1
CapsuleOral50 MG
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
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
US9169235No2004-03-122024-03-12US flag
Additional Data Available
  • Filed On
    Filed On
    Available for Purchase

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
Not Available
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

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
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. [PubMed:25981132]
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
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. [PubMed:25981132]
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. [PubMed:25981132]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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. [PubMed:25981132]
  2. Linparza (olaparib) drug monograph [File]
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. [PubMed:25981132]
  2. Olaparib Health Canada Product Monograph [File]
  3. Olaparib EMA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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

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. Olaparib New Zealand Data Sheet [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. Olaparib New Zealand Data Sheet [Link]

Drug created on May 14, 2015 14:38 / Updated on November 25, 2020 08:52

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