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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 PARP2.8,9,13 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.8,9,13 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
Structure for Olaparib (DB09074)
- 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
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
It is also indicated in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC).14
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Advanced epithelial ovarian cancer Regimen in combination with: Bevacizumab (DB00112) •••••••••••• ••••• •••••••••• •• •••••••••••••• ••••••••••••• •••••••• •••••••••• ••••••••••••• •••••••••• ••••••••••••• •••••••••• ••••• •••••• Treatment of Advanced epithelial ovarian cancer •••••••••••• ••••• •••••••• •••••••••• ••••••••••••• •••••••••• •• •••••••••••••• •••••••••••• •••••• Used in combination to treat Advanced fallopian tube carcinoma Regimen in combination with: Bevacizumab (DB00112) •••••••••••• ••••• •••••••••• ••••••••••••• •••••••••• •••••• •••••••• •••••••••• ••••••••••••• •••••••••• •• •••••••••••••• •••••••••••• •••••• Treatment of Advanced fallopian tube carcinoma •••••••••••• ••••• •••••••••• •• •••••••••••••• ••••••••••••• •••••••• •••••••••• •••••••••••• •••••• Used in combination to treat Advanced primary peritoneal carcinoma Regimen in combination with: Bevacizumab (DB00112) •••••••••••• ••••• •••••••• •••••••••• ••••••••••••• •••••••••• ••••••••••••• •••••••••• •••••• •••••••••• •• •••••••••••••• •••••••••••• •••••• - Associated Therapies
- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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 essential 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
Target Actions Organism APoly [ADP-ribose] polymerase 1 inhibitorHumans APoly [ADP-ribose] polymerase 2 inhibitorHumans AProtein mono-ADP-ribosyltransferase PARP3 inhibitorHumans UAldo-keto reductase family 1 member C3 inhibitorHumans - 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
Hover over products below to view reaction partners
- 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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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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Olaparib can be increased when it is combined with Abametapir. Abatacept The metabolism of Olaparib can be increased when combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Olaparib. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Olaparib. Acalabrutinib The metabolism of Acalabrutinib can be decreased when combined with Olaparib. - 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
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Lynparza Tablet, film coated 150 mg Oral Astrazeneca Ab 2021-02-10 Not applicable EU 
Lynparza Tablet, film coated 100 mg Oral Astrazeneca Ab 2021-02-10 Not applicable EU Lynparza Capsule 50 mg Oral Astrazeneca Ab 2016-05-16 2021-01-11 Canada 
Lynparza Capsule 50 mg/1 Oral AstraZeneca Pharmaceuticals LP 2014-12-24 2020-03-31 US 
Lynparza Tablet 150 mg Oral Astrazeneca Ab 2018-05-23 Not applicable Canada
Categories
- ATC Codes
- L01XK01 — Olaparib
- Drug Categories
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Inhibitors
- Cytochrome P-450 CYP2B6 Inducers
- Cytochrome P-450 CYP2B6 Inducers (strength unknown)
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strength unknown)
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A5 Inducers
- Cytochrome P-450 CYP3A5 Inducers (strength unknown)
- Cytochrome P-450 CYP3A5 Inhibitors
- Cytochrome P-450 CYP3A5 Inhibitors (weak)
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Enzyme Inhibitors
- Immunosuppressive Agents
- MATE 1 Inhibitors
- MATE 2-K Inhibitors
- MATE inhibitors
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- OAT3/SLC22A8 Inhibitors
- OATP1B1/SLCO1B1 Inhibitors
- OCT1 inhibitors
- OCT2 Inhibitors
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Poly (ADP-ribose) polymerase (PARP) inhibitors
- Poly(ADP-ribose) Polymerase Inhibitors
- Pyridazines
- UGT1A1 Inhibitors
- 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
- Solimando DA Jr, Waddell JA: Nivolumab and Olaparib. Hosp Pharm. 2015 May;50(5):356-66. doi: 10.1310/hpj5005-356. [Article]
- 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]
- 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]
- 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]
- Deeks ED: Olaparib: first global approval. Drugs. 2015 Feb;75(2):231-40. doi: 10.1007/s40265-015-0345-6. [Article]
- 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]
- New Zealand Data Sheet: LYNPARZA (olaparib) Oral Capsules [Link]
- FDA Approved Drug Products: LYNPARZA (olaparib) tablets, for oral use [Link]
- FDA Approved Drug Products: LYNPARZA (olaparib) capsules, for oral use [Link]
- Astrazeneca: Lynparza (Olaparib) MSDS [Link]
- EMA Approved Drug Products: Lynparza (olaparib) Oral Tablets (March 2023) [Link]
- Health Canada Approved Drug Products: LYNPARZA (Olaparib) Oral Tablets [Link]
- FDA Approved Drug Products: LYNPARZA (olaparib) tablets, for oral use (October 2022) [Link]
- FDA Approved Drug Products: LYNPARZA (olaparib) tablets, for oral use (May 2023) [Link]
- Health Canada Approved Drug Products: LYNPARZA (Olaparib) Tablets, for oral use (July 2023) [Link]
- FDA Approved Drug Products: LYNPARZA (olaparib) tablets, for oral use (September 2023) [Link]
- External Links
- Human Metabolome Database
- HMDB0255929
- KEGG Drug
- D09730
- ChemSpider
- 23343272
- BindingDB
- 27566
- 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 / 8hlj
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Not Available Ovarian Cancer 1 somestatus stop reason just information to hide Not Available Approved for Marketing Not Available Ovarian Cancer 1 somestatus stop reason just information to hide Not Available Completed Not Available Cancer 2 somestatus stop reason just information to hide Not Available Completed Not Available Endometrial Carcinoma 1 somestatus stop reason just information to hide Not Available Completed Not Available Relapsed Ovarian Cancers Patients 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 50 mg/1 Tablet Oral 100 mg Tablet Oral 100.00 mg Tablet Oral 150 mg Tablet, film coated Oral 100 mg/1 Tablet, film coated Oral 150 mg/1 Tablet, coated Oral 100 mg Tablet, coated Oral 150 mg Tablet, film coated Oral 100 mg Tablet, film coated Oral 150 mg Tablet, coated Oral 10000000 mg Tablet, coated Oral 15000000 mg Capsule Oral 50 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8859562 No 2014-10-14 2031-08-04 US US8912187 No 2014-12-16 2024-03-12 US US8143241 No 2012-03-27 2027-08-12 US US7449464 No 2008-11-11 2024-10-11 US US8247416 No 2012-08-21 2028-09-24 US US7151102 No 2006-12-19 2022-04-29 US US7981889 No 2011-07-19 2024-10-11 US US8071579 No 2011-12-06 2027-08-12 US US8475842 No 2013-07-02 2029-12-31 US US9566276 No 2017-02-14 2024-03-12 US US9169235 No 2015-10-27 2024-03-12 US US11633396 No 2009-10-07 2029-10-07 US US11970530 No 2021-10-25 2041-10-25 US US11975001 No 2009-10-07 2029-10-07 US US12048695 No 2009-10-07 2029-10-07 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 198 https://www.fishersci.com/store/msds?partNumber=AC466292500&productDescription=OLAPARIB+250MG&vendorId=VN00032119&countryCode=US&language=en - Predicted Properties
Property Value Source Water Solubility 0.0601 mg/mL ALOGPS logP 2.72 ALOGPS logP 1.96 Chemaxon logS -3.9 ALOGPS pKa (Strongest Acidic) 9.96 Chemaxon pKa (Strongest Basic) -0.9 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 82.08 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 117.53 m3·mol-1 Chemaxon Polarizability 43.81 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-000i-0000900000-df0c8471ea03eb034288 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-03e9-0010900000-9b986d0eb78d67f8bc45 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0049300000-c076cf4f37f83404c4c5 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-1103900000-d1703e8e4a0b4c2e871d Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-00lr-1294300000-f7d96859de2acd8094f6 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-066u-6839400000-2c8c12f9777a6c96d663 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 203.74748 predictedDeepCCS 1.0 (2019) [M+H]+ 206.10548 predictedDeepCCS 1.0 (2019) [M+Na]+ 212.39412 predictedDeepCCS 1.0 (2019)
Targets
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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
- Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18055453, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:20388712, PubMed:21680843, PubMed:22582261, PubMed:23230272, PubMed:25043379, PubMed:26344098, PubMed:26626479, PubMed:26626480, PubMed:30104678, PubMed:31796734, PubMed:32028527, PubMed:32241924, PubMed:32358582, PubMed:33186521, PubMed:34465625, PubMed:34737271). Mediates glutamate, aspartate, serine, histidine or tyrosine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units (PubMed:19764761, PubMed:25043379, PubMed:28190768, PubMed:29954836, PubMed:35393539, PubMed:7852410, PubMed:9315851). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:33186521, PubMed:34874266). Specificity for the different amino acids is conferred by interacting factors, such as HPF1 and NMNAT1 (PubMed:28190768, PubMed:29954836, PubMed:32028527, PubMed:33186521, PubMed:33589610, PubMed:34625544, PubMed:34874266). Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 confers serine specificity by completing the PARP1 active site (PubMed:28190768, PubMed:29954836, PubMed:32028527, PubMed:33186521, PubMed:33589610, PubMed:34625544, PubMed:34874266). Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1 (PubMed:29954836, PubMed:30257210). Following interaction with NMNAT1, catalyzes glutamate and aspartate ADP-ribosylation of target proteins; NMNAT1 confers glutamate and aspartate specificity (By similarity). PARP1 initiates the repair of DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones (H2BS6ADPr and H3S10ADPr), thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks (PubMed:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:23230272, PubMed:27067600, PubMed:34465625, PubMed:34874266). HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP1 in order to limit the length of poly-ADP-ribose chains (PubMed:33683197, PubMed:34732825, PubMed:34795260). In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair: together with TIMELESS, accumulates at DNA damage sites and promotes homologous recombination repair by mediating poly-ADP-ribosylation (PubMed:26344098, PubMed:30356214). Mediates the poly-ADP-ribosylation of a number of proteins, including itself, APLF, CHFR, RPA1 and NFAT5 (PubMed:17396150, PubMed:19764761, PubMed:24906880, PubMed:34049076). In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2'-OH group in single- and double-stranded DNA, respectively (PubMed:27471034). Required for PARP9 and DTX3L recruitment to DNA damage sites (PubMed:23230272). PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (PubMed:23230272). PARP1-mediated DNA repair in neurons plays a role in sleep: senses DNA damage in neurons and promotes sleep, facilitating efficient DNA repair (By similarity). In addition to DNA repair, also involved in other processes, such as transcription regulation, programmed cell death, membrane repair, adipogenesis and innate immunity (PubMed:15607977, PubMed:17177976, PubMed:19344625, PubMed:27256882, PubMed:32315358, PubMed:32844745, PubMed:35124853, PubMed:35393539, PubMed:35460603). Acts as a repressor of transcription: binds to nucleosomes and modulates chromatin structure in a manner similar to histone H1, thereby altering RNA polymerase II (PubMed:15607977, PubMed:22464733). Acts both as a positive and negative regulator of transcription elongation, depending on the context (PubMed:27256882, PubMed:35393539). Acts as a positive regulator of transcription elongation by mediating poly-ADP-ribosylation of NELFE, preventing RNA-binding activity of NELFE and relieving transcription pausing (PubMed:27256882). Acts as a negative regulator of transcription elongation in response to DNA damage by catalyzing poly-ADP-ribosylation of CCNT1, disrupting the phase separation activity of CCNT1 and subsequent activation of CDK9 (PubMed:35393539). Involved in replication fork progression following interaction with CARM1: mediates poly-ADP-ribosylation at replication forks, slowing fork progression (PubMed:33412112). Poly-ADP-ribose chains generated by PARP1 also play a role in poly-ADP-ribose-dependent cell death, a process named parthanatos (By similarity). Also acts as a negative regulator of the cGAS-STING pathway (PubMed:32315358, PubMed:32844745, PubMed:35460603). Acts by mediating poly-ADP-ribosylation of CGAS: PARP1 translocates into the cytosol following phosphorylation by PRKDC and catalyzes poly-ADP-ribosylation and inactivation of CGAS (PubMed:35460603). Acts as a negative regulator of adipogenesis: catalyzes poly-ADP-ribosylation of histone H2B on 'Glu-35' (H2BE35ADPr) following interaction with NMNAT1, inhibiting phosphorylation of H2B at 'Ser-36' (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (By similarity). Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257)
- Specific Function
- chromatin binding
- Gene Name
- PARP1
- Uniprot ID
- P09874
- Uniprot Name
- Poly [ADP-ribose] polymerase 1
- Molecular Weight
- 113082.945 Da
References
- 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]
- 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]
- 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
- Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:10364231, PubMed:25043379, PubMed:27471034, PubMed:30104678, PubMed:32028527, PubMed:32939087, PubMed:34108479, PubMed:34486521, PubMed:34874266). Mediates glutamate, aspartate or serine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units (PubMed:25043379, PubMed:30104678, PubMed:30321391). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:32939087). Mediates glutamate and aspartate ADP-ribosylation of target proteins in absence of HPF1 (PubMed:25043379). Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 conferring serine specificity by completing the PARP2 active site (PubMed:28190768, PubMed:32028527, PubMed:34108479, PubMed:34486521, PubMed:34874266). PARP2 initiates the repair of double-strand DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones, thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks (PubMed:10364231, PubMed:32939087, PubMed:34108479). HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP2 in order to limit the length of poly-ADP-ribose chains (PubMed:34732825, PubMed:34795260). Specifically mediates formation of branched poly-ADP-ribosylation (PubMed:30104678). Branched poly-ADP-ribose chains are specifically recognized by some factors, such as APLF (PubMed:30104678). In addition to proteins, also able to ADP-ribosylate DNA: preferentially acts on 5'-terminal phosphates at DNA strand breaks termini in nicked duplex (PubMed:27471034, PubMed:29361132)
- Specific Function
- chromatin binding
- Gene Name
- PARP2
- Uniprot ID
- Q9UGN5
- Uniprot Name
- Poly [ADP-ribose] polymerase 2
- Molecular Weight
- 66205.31 Da
References
- 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]
- 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
- Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins and plays a key role in the response to DNA damage (PubMed:16924674, PubMed:19354255, PubMed:20064938, PubMed:21211721, PubMed:21270334, PubMed:23742272, PubMed:24598253, PubMed:25043379, PubMed:28447610). Mediates mono-ADP-ribosylation of glutamate, aspartate or lysine residues on target proteins (PubMed:20064938, PubMed:25043379). In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation (PubMed:25043379). Involved in DNA repair by mediating mono-ADP-ribosylation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism, such as histone H2B, XRCC5 and XRCC6 (PubMed:16924674, PubMed:24598253). ADP-ribosylation follows DNA damage and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks (PubMed:16924674, PubMed:21211721, PubMed:21270334). Involved in single-strand break repair by catalyzing mono-ADP-ribosylation of histone H2B on 'Glu-2' (H2BE2ADPr) of nucleosomes containing nicked DNA (PubMed:27530147). Cooperates with the XRCC5-XRCC6 (Ku80-Ku70) heterodimer to limit end-resection thereby promoting accurate NHEJ (PubMed:24598253). Suppresses G-quadruplex (G4) structures in response to DNA damage (PubMed:28447610). Associates with a number of DNA repair factors and is involved in the response to exogenous and endogenous DNA strand breaks (PubMed:16924674, PubMed:21211721, PubMed:21270334). Together with APLF, promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ) (PubMed:21211721). May link the DNA damage surveillance network to the mitotic fidelity checkpoint (PubMed:16924674). Acts as a negative regulator of immunoglobulin class switch recombination, probably by controlling the level of AICDA /AID on the chromatin (By similarity). In addition to proteins, also able to ADP-ribosylate DNA: mediates DNA mono-ADP-ribosylation of DNA strand break termini via covalent addition of a single ADP-ribose moiety to a 5'- or 3'-terminal phosphate residues in DNA containing multiple strand breaks (PubMed:29361132, PubMed:29520010)
- Specific Function
- catalytic activity
- Gene Name
- PARP3
- Uniprot ID
- Q9Y6F1
- Uniprot Name
- Protein mono-ADP-ribosyltransferase PARP3
- Molecular Weight
- 60088.74 Da
References
- 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
- Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids. Acts as a NAD(P)(H)-dependent 3-, 17- and 20-ketosteroid reductase on the steroid nucleus and side chain and regulates the metabolism of androgens, estrogens and progesterone (PubMed:10622721, PubMed:11165022, PubMed:7650035, PubMed:9415401, PubMed:9927279). Displays the ability to catalyze both oxidation and reduction in vitro, but most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentration of NADPH (PubMed:11165022, PubMed:14672942). Acts preferentially as a 17-ketosteroid reductase and has the highest catalytic efficiency of the AKR1C enzyme for the reduction of delta4-androstenedione to form testosterone (PubMed:20036328). Reduces prostaglandin (PG) D2 to 11beta-prostaglandin F2, progesterone to 20alpha-hydroxyprogesterone and estrone to 17beta-estradiol (PubMed:10622721, PubMed:10998348, PubMed:11165022, PubMed:15047184, PubMed:19010934, PubMed:20036328). Catalyzes the transformation of the potent androgen dihydrotestosterone (DHT) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol (3-alpha-diol) (PubMed:10557352, PubMed:10998348, PubMed:11165022, PubMed:14672942, PubMed:7650035, PubMed:9415401). Also displays retinaldehyde reductase activity toward 9-cis-retinal (PubMed:21851338)
- Specific Function
- 15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity
- Gene Name
- AKR1C3
- Uniprot ID
- P42330
- Uniprot Name
- Aldo-keto reductase family 1 member C3
- Molecular Weight
- 36852.89 Da
References
- 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
- SubstrateInhibitor
- Curator comments
- In vitro, olaparib (17-500 μM) inhibited CYP3A4/5 with an IC50 of 119 μM.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- 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]
- 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]
- 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]
- FDA Approved Drug Products: LYNPARZA (olaparib) tablets, for oral use [Link]
- Linparza (olaparib) drug monograph [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- In vitro, olaparib (17-500 μM) inhibited CYP3A4/5 with an IC50 of 119 μM.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
- Specific Function
- aromatase activity
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- 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]
- FDA Approved Drug Products: LYNPARZA (olaparib) tablets, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:12865317, PubMed:21289075). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:12865317, PubMed:21289075). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850)
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- 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]
- Olaparib Health Canada Product Monograph [File]
- Olaparib EMA Label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15472229, PubMed:18004206, PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004206, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:15472229, PubMed:18719240, PubMed:23288867). Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (PubMed:17187418, PubMed:18004206, PubMed:19830808, PubMed:24525562). Also catalyzes the glucuronidation the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:18004212, PubMed:20610558)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1A1
- Molecular Weight
- 59590.91 Da
References
- New Zealand Data Sheet: LYNPARZA (olaparib) Oral Capsules [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- New Zealand Data Sheet: LYNPARZA (olaparib) Oral Capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Functions as a 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 the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction
- Specific Function
- Not Available
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23539.43 Da
References
- New Zealand Data Sheet: LYNPARZA (olaparib) Oral Capsules [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- 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
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- New Zealand Data Sheet: LYNPARZA (olaparib) Oral Capsules [Link]
Drug created at May 14, 2015 20:38 / Updated at October 10, 2024 16:27