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Similarity based on WHO Anatomical Therapeutic Chemical (ATC) classification and NHS BNF section grouping. Source data: NHS dm+d via TRUD (OGL v3.0), WHO ATC/DDD Index.
NHS prescribing volume and spending trends
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Clinical guidelines and formulary information
British National Formulary
Olaparib
BNF
Drug monograph — bnf.nice.org.ukSource: British National Formulary, NICE. Joint Formulary Committee. Contains public sector information licensed under the Open Government Licence v3.0.
NICE clinical guidance(14)
Olaparib with abiraterone for untreated hormone-relapsed metastatic prostate cancer (TA951)
TA951
Technology appraisal
Updated Feb 2024Olaparib for previously treated BRCA mutation-positive hormone-relapsed metastatic prostate cancer (TA887)
TA887
Technology appraisal
Updated May 2023Olaparib for treating BRCA mutation-positive HER2-negative advanced breast cancer after chemotherapy (TA1040)
TA1040
Technology appraisal
Updated Feb 2025Olaparib with bevacizumab for maintenance treatment of advanced high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer (TA946)
TA946
Technology appraisal
Updated Jan 2024Olaparib for adjuvant treatment of BRCA mutation-positive HER2-negative high-risk early breast cancer after chemotherapy (TA886)
TA886
Technology appraisal
Updated May 2023Olaparib for maintenance treatment of relapsed, platinum-sensitive ovarian, fallopian tube or peritoneal cancer after 2 or more courses of platinum-based chemotherapy (TA908)
TA908
Technology appraisal
Updated Jul 2023Olaparib for maintenance treatment of BRCA mutation-positive advanced ovarian, fallopian tube or peritoneal cancer after response to first-line platinum-based chemotherapy (TA962)
TA962
Technology appraisal
Updated Mar 2024Olaparib for maintenance treatment of BRCA mutation-positive metastatic pancreatic cancer after platinum-based chemotherapy (terminated appraisal) (TA750)
TA750
Technology appraisal
Updated Dec 2021Ovarian cancer: recognition and initial management (CG122)
CG122
Clinical guideline
Updated Oct 2023Niraparib for maintenance treatment of advanced ovarian, fallopian tube and peritoneal cancer after response to first-line platinum-based chemotherapy (TA1129)
TA1129
Technology appraisal
Updated Feb 2026Rucaparib for maintenance treatment of advanced ovarian, fallopian tube and peritoneal cancer after response to first-line platinum-based chemotherapy (TA1055)
TA1055
Technology appraisal
Updated Apr 2025Talazoparib with enzalutamide for untreated hormone-relapsed metastatic prostate cancer (TA1130)
TA1130
Technology appraisal
Updated Feb 2026Rucaparib for maintenance treatment of relapsed platinum-sensitive ovarian, fallopian tube or peritoneal cancer (TA1007)
TA1007
Technology appraisal
Updated Sept 2024Niraparib for maintenance treatment of relapsed, platinum-sensitive ovarian, fallopian tube and peritoneal cancer (TA784)
TA784
Technology appraisal
Updated Apr 2022Source: National Institute for Health and Care Excellence (NICE). Contains public sector information licensed under the Open Government Licence v3.0.
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Supply & product information
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Codes for healthcare professionals and prescribing systems
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NHS UK identifiers
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SNOMED CT and dm+d codes from NHS TRUD (Technology Reference data Update Distribution), licensed under the Open Government Licence v3.0. BNF codes from NHS Business Services Authority (NHSBSA). ATC codes from the WHO Collaborating Centre for Drug Statistics Methodology (whocc.no).
Active and completed clinical studies from ClinicalTrials.gov
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Searching UK clinical trials...
Source: ClinicalTrials.gov, a database of the U.S. National Library of Medicine (NLM), National Institutes of Health (NIH). Data accessed via ClinicalTrials.gov API v2. Trial information is provided for research purposes and does not constitute medical advice.
Pharmacology and chemical data from DrugBank
Key facts
Drug status
Approved
Major interactions
None known
Half-life
6.10 hours
Mechanism
Poly(ADP-ribose) polymerases (PARPs) are multifunctional enzymes comprising 17 members.
Food interactions
3 warnings
Human targets
4 targets
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
300 mg
Following oral administration, olaparib is rapidly absorbed.
[A35290]
After administration of a single 300 mg dose of olaparib, the mean (CV%) Cmax was 5.4…
[A35290]
After administration of a single 300 mg dose of olaparib, the mean (CV%) Cmax was 5.4…
Half-life
6.10 hours
Following a single oral dose in patients with cancer, the mean terminal half-life was 6.10 hours.
[A246025]
[A246025]
Protein binding
82%
The protein binding of olaparib is approximately 82% in vitro.
[L41100]…
[L41100]…
Volume of distribution
136 L
The mean (± standard deviation) apparent volume of distribution of olaparib is 158 ± 136 L following a single 300 mg dose.
[L41100]
[L41100]
Metabolism
70%
Olaparib is metabolized by cytochrome P450 (CYP) 3A4/5 in vitro.…
Elimination
86%
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.…
Clearance
4.55 L/h
Following a single oral dose in patients with cancer, the mean apparent plasma clearance was 4.55 L/h.
[A246025]
[A246025]
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Status:
Approved
Investigational
Small molecule
About this compound
Olaparib is a selective and potent inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, PARP1 and PARP2.[L41100][L40908][L43792] 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.[A246015]
Olaparib is used to treat a number of BRCA-associated tumours, including ovarian cancer, breast cancer, pancreatic cancer, and prostate cancer.[L41100][L40908][L43792] It was first approved by the FDA and EU in December 2014,[A246020] and by Health Canada in April 2016.[L42820]
Olaparib is used to treat a number of BRCA-associated tumours, including ovarian cancer, breast cancer, pancreatic cancer, and prostate cancer.[L41100][L40908][L43792] It was first approved by the FDA and EU in December 2014,[A246020] and by Health Canada in April 2016.[L42820]
Properties:
solid
Avg. mass: 434.46 Da
DrugBank 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.
[L41100][L42695]
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.
[L41100][L42695]
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.
[L41100][L42695]
Breast cancer
Olaparib is indicated for the adjuvant treatment of adult patients with deleterious or suspected deleterious g_BRCA_m human epidermal growth factor receptor 2 (HER2)-negative high risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy.
[L41100][L42695][L42820]
Olaparib is indicated for the treatment of adult patients with deleterious or suspected deleterious g_BRCA_m, 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.
[L41100][L42695]
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.
[L41100][L42695]
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,[L42695] such as [enzalutamide] or [abiraterone].
[L41100]
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).
[L46971]
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.
[L41100][L42695]
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.
[L41100][L42695]
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.
[L41100][L42695]
Breast cancer
Olaparib is indicated for the adjuvant treatment of adult patients with deleterious or suspected deleterious g_BRCA_m human epidermal growth factor receptor 2 (HER2)-negative high risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy.
[L41100][L42695][L42820]
Olaparib is indicated for the treatment of adult patients with deleterious or suspected deleterious g_BRCA_m, 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.
[L41100][L42695]
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.
[L41100][L42695]
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,[L42695] such as [enzalutamide] or [abiraterone].
[L41100]
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).
[L46971]
Also known as(116)
4-(3-{[4-(cyclopropylcarbonyl)piperazin-1-yl]carbonyl}-4-fluorobenzyl)phthalazin-1(2H)-one
Olaparib
2.4.2.30
ADP-ribosyltransferase diphtheria toxin-like 1
ADPRT
ADPRT 1
ARTD1
DNA ADP-ribosyltransferase PARP1
Dosage forms(14)
(Oral) — 50 mg
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
Molecular properties(19)
Drug interactions(1025)
Known interactions with other medications. Always consult a healthcare professional.
The risk or severity of adverse effects can be increased when Denosumab is combined with Olaparib.
Peginterferon alfa-2a
Unknown severity
The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Olaparib.
Interferon alfa-n1
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Olaparib.
Interferon alfa-n3
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Olaparib.
Peginterferon alfa-2b
Unknown severity
The risk or severity of adverse effects can be increased when Peginterferon alfa-2b is combined with Olaparib.
Interferon gamma-1b
Unknown severity
The risk or severity of adverse effects can be increased when Interferon gamma-1b is combined with Olaparib.
Interferon alfa-2a
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfa-2a is combined with Olaparib.
Gemtuzumab ozogamicin
Unknown severity
The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Olaparib.
Pegaspargase
Unknown severity
The risk or severity of adverse effects can be increased when Pegaspargase is combined with Olaparib.
Interferon beta-1b
Unknown severity
The risk or severity of adverse effects can be increased when Interferon beta-1b is combined with Olaparib.
Interferon alfacon-1
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Olaparib.
The risk or severity of adverse effects can be increased when Rituximab is combined with Olaparib.
Basiliximab
Unknown severity
The risk or severity of adverse effects can be increased when Basiliximab is combined with Olaparib.
The risk or severity of adverse effects can be increased when Muromonab is combined with Olaparib.
Ibritumomab tiuxetan
Unknown severity
The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Olaparib.
Tositumomab
Unknown severity
The risk or severity of adverse effects can be increased when Tositumomab is combined with Olaparib.
Alemtuzumab
Unknown severity
The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Olaparib.
The risk or severity of adverse effects can be increased when Alefacept is combined with Olaparib.
Efalizumab
Unknown severity
The risk or severity of adverse effects can be increased when Efalizumab is combined with Olaparib.
Antithymocyte immunoglobulin (rabbit)
Unknown severity
The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Olaparib.
Interferon alfa-2b
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfa-2b is combined with Olaparib.
Daclizumab
Unknown severity
The risk or severity of adverse effects can be increased when Daclizumab is combined with Olaparib.
Phenylalanine
Unknown severity
The risk or severity of adverse effects can be increased when Phenylalanine is combined with Olaparib.
Cladribine
Moderate
Olaparib may increase the immunosuppressive activities of Cladribine.
Carmustine
Unknown severity
The risk or severity of adverse effects can be increased when Carmustine is combined with Olaparib.
The risk or severity of adverse effects can be increased when Amsacrine is combined with Olaparib.
The risk or severity of adverse effects can be increased when Bleomycin is combined with Olaparib.
Chlorambucil
Unknown severity
The risk or severity of adverse effects can be increased when Chlorambucil is combined with Olaparib.
Raltitrexed
Unknown severity
The risk or severity of adverse effects can be increased when Raltitrexed is combined with Olaparib.
The risk or severity of adverse effects can be increased when Mitomycin is combined with Olaparib.
Floxuridine
Unknown severity
The risk or severity of adverse effects can be increased when Floxuridine is combined with Olaparib.
Indomethacin
Unknown severity
The risk or severity of adverse effects can be increased when Indomethacin is combined with Olaparib.
Tioguanine
Unknown severity
The risk or severity of adverse effects can be increased when Tioguanine is combined with Olaparib.
Dexrazoxane
Unknown severity
The risk or severity of adverse effects can be increased when Dexrazoxane is combined with Olaparib.
Streptozocin
Unknown severity
The risk or severity of adverse effects can be increased when Streptozocin is combined with Olaparib.
Trifluridine
Unknown severity
The risk or severity of adverse effects can be increased when Trifluridine is combined with Olaparib.
Gemcitabine
Unknown severity
The risk or severity of adverse effects can be increased when Gemcitabine is combined with Olaparib.
Epirubicin
Unknown severity
The risk or severity of adverse effects can be increased when Epirubicin is combined with Olaparib.
Lenalidomide
Unknown severity
The risk or severity of adverse effects can be increased when Lenalidomide is combined with Olaparib.
Altretamine
Unknown severity
The risk or severity of adverse effects can be increased when Altretamine is combined with Olaparib.
Zidovudine
Unknown severity
The risk or severity of adverse effects can be increased when Zidovudine is combined with Olaparib.
The risk or severity of adverse effects can be increased when Cisplatin is combined with Olaparib.
Oxaliplatin
Unknown severity
The risk or severity of adverse effects can be increased when Oxaliplatin is combined with Olaparib.
Fluorouracil
Unknown severity
The risk or severity of adverse effects can be increased when Fluorouracil is combined with Olaparib.
Propylthiouracil
Unknown severity
The risk or severity of adverse effects can be increased when Propylthiouracil is combined with Olaparib.
Pentostatin
Unknown severity
The risk or severity of adverse effects can be increased when Pentostatin is combined with Olaparib.
The risk or severity of adverse effects can be increased when Linezolid is combined with Olaparib.
Clofarabine
Unknown severity
The risk or severity of adverse effects can be increased when Clofarabine is combined with Olaparib.
Prednisone
Unknown severity
The risk or severity of adverse effects can be increased when Prednisone is combined with Olaparib.
Pemetrexed
Unknown severity
The risk or severity of adverse effects can be increased when Pemetrexed is combined with Olaparib.
Showing 50 of 1025 interactions
Food & lifestyle interactions
Avoid Grapefruit
Avoid grapefruit products. Grapefruit inhibits the CYP3A metabolism of olaparib, which may increase its serum concentration.
Advice
Avoid St. John's Wort. This herb induces the CYP3A metabolism of olaparib and may reduce its serum concentration.
Advice
Take with or without food. Food does not significantly alter the extent of olaparib absorption.
Toxicity & overdose
The oral LD50 in rats is approximately 240-300 mg/kg.
[L41110]
There is limited information regarding the overdose of olaparib.
[L41110]
There is limited information regarding the overdose of olaparib.
How it works
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.[L41100] 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.[A245985]
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.[A246015] 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.[A245985]
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.[L41100]
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.[A246015] 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.[A245985]
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.[L41100]
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.[L41100]
In preclinical models of cancer, olaparib demonstrated anti-tumour activity when used alone, in combination with chemotherapeutic agents, or radiotherapy.[A246020] 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.[A245985][A246015]
In preclinical models of cancer, olaparib demonstrated anti-tumour activity when used alone, in combination with chemotherapeutic agents, or radiotherapy.[A246020] 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.[A245985][A246015]
Pharmacokinetics
How the body processes this drug — absorption, distribution, metabolism, and elimination
Absorption
Following oral administration, olaparib is rapidly absorbed.
[A35290]
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.
[L41100]
[A35290]
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.
[L41100]
Half-life
Following a single oral dose in patients with cancer, the mean terminal half-life was 6.10 hours.
[A246025]
[A246025]
Protein binding
The protein binding of olaparib is approximately 82% in vitro.
[L41100]
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%.
[L5089]
[L41100]
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%.
[L5089]
Volume of distribution
The mean (± standard deviation) apparent volume of distribution of olaparib is 158 ± 136 L following a single 300 mg dose.
[L41100]
[L41100]
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.
[L41100]
In humans, olaparib can also undergo hydrolysis, hydroxylation, and dehydrogenation.
[A246000]
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.
[L5089]
[L41100]
In humans, olaparib can also undergo hydrolysis, hydroxylation, and dehydrogenation.
[A246000]
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.
[L5089]
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.
[L41100]
[L41100]
Clearance
Following a single oral dose in patients with cancer, the mean apparent plasma clearance was 4.55 L/h.
[A246025]
[A246025]
Drug targets(4)
Proteins and enzymes this drug interacts with in the body
Poly [ADP-ribose] polymerase 1
PARP1
inhibitor
Specific functionchromatin binding
Cellular location
Chromosome
General function & pharmacology
Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair .
PMID:17177976 PMID:18055453 PMID:18172500 PMID:19344625 PMID:19661379 PMID:20388712 PMID:21680843 PMID:22582261 PMID:23230272 PMID:25043379 PMID:26344098 PMID:26626479 PMID:26626480 PMID:30104678 PMID:31796734 PMID:32028527 PMID:32241924 PMID:32358582 PMID:33186521 PMID:34465625 PMID: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 .
PMID:19764761 PMID:25043379 PMID:28190768 PMID:29954836 PMID:35393539 PMID:7852410 PMID:9315851
Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage .
PMID:33186521 PMID:34874266
Specificity for the different amino acids is conferred by interacting factors, such as HPF1 and NMNAT1 .
PMID:28190768 PMID:29954836 PMID:32028527 PMID:33186521 PMID:33589610 PMID:34625544 PMID:34874266
Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 confers serine specificity by completing the PARP1 active site .
PMID:28190768 PMID:29954836 PMID:32028527 PMID:33186521 PMID:33589610 PMID:34625544 PMID:34874266
Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1 .
PMID:29954836 PMID: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 .
PMID:17177976 PMID:18172500 PMID:19344625 PMID:19661379 PMID:23230272 PMID:27067600 PMID:34465625 PMID:34874266
HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP1 in order to limit the length of poly-ADP-ribose chains .
PMID:33683197 PMID:34732825 PMID: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 .
PMID:26344098 PMID:30356214
Mediates the poly-ADP-ribosylation of a number of proteins, including itself, APLF, CHFR, RPA1 and NFAT5 .
PMID:17396150 PMID:19764761 PMID:24906880 PMID: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 .
PMID:27471034
Required for PARP9 and DTX3L recruitment to DNA damage sites .
PMID:23230272
PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites .
PMID: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 .
PMID:15607977 PMID:17177976 PMID:19344625 PMID:27256882 PMID:32315358 PMID:32844745 PMID:35124853 PMID:35393539 PMID: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 .
PMID:15607977 PMID:22464733
Acts both as a positive and negative regulator of transcription elongation, depending on the context .
PMID:27256882 PMID: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 .
PMID: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 .
PMID:35393539
Involved in replication fork progression following interaction with CARM1: mediates poly-ADP-ribosylation at replication forks, slowing fork progression .
PMID: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 .
PMID:32315358 PMID:32844745 PMID: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 .
PMID: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 .
PMID:27257257
Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming PMID:27257257
PMID:17177976 PMID:18055453 PMID:18172500 PMID:19344625 PMID:19661379 PMID:20388712 PMID:21680843 PMID:22582261 PMID:23230272 PMID:25043379 PMID:26344098 PMID:26626479 PMID:26626480 PMID:30104678 PMID:31796734 PMID:32028527 PMID:32241924 PMID:32358582 PMID:33186521 PMID:34465625 PMID: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 .
PMID:19764761 PMID:25043379 PMID:28190768 PMID:29954836 PMID:35393539 PMID:7852410 PMID:9315851
Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage .
PMID:33186521 PMID:34874266
Specificity for the different amino acids is conferred by interacting factors, such as HPF1 and NMNAT1 .
PMID:28190768 PMID:29954836 PMID:32028527 PMID:33186521 PMID:33589610 PMID:34625544 PMID:34874266
Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 confers serine specificity by completing the PARP1 active site .
PMID:28190768 PMID:29954836 PMID:32028527 PMID:33186521 PMID:33589610 PMID:34625544 PMID:34874266
Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1 .
PMID:29954836 PMID: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 .
PMID:17177976 PMID:18172500 PMID:19344625 PMID:19661379 PMID:23230272 PMID:27067600 PMID:34465625 PMID:34874266
HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP1 in order to limit the length of poly-ADP-ribose chains .
PMID:33683197 PMID:34732825 PMID: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 .
PMID:26344098 PMID:30356214
Mediates the poly-ADP-ribosylation of a number of proteins, including itself, APLF, CHFR, RPA1 and NFAT5 .
PMID:17396150 PMID:19764761 PMID:24906880 PMID: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 .
PMID:27471034
Required for PARP9 and DTX3L recruitment to DNA damage sites .
PMID:23230272
PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites .
PMID: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 .
PMID:15607977 PMID:17177976 PMID:19344625 PMID:27256882 PMID:32315358 PMID:32844745 PMID:35124853 PMID:35393539 PMID: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 .
PMID:15607977 PMID:22464733
Acts both as a positive and negative regulator of transcription elongation, depending on the context .
PMID:27256882 PMID: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 .
PMID: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 .
PMID:35393539
Involved in replication fork progression following interaction with CARM1: mediates poly-ADP-ribosylation at replication forks, slowing fork progression .
PMID: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 .
PMID:32315358 PMID:32844745 PMID: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 .
PMID: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 .
PMID:27257257
Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming PMID:27257257
Poly [ADP-ribose] polymerase 2
PARP2
inhibitor
Specific functionchromatin binding
Cellular location
Nucleus
General function & pharmacology
Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair .
PMID:10364231 PMID:25043379 PMID:27471034 PMID:30104678 PMID:32028527 PMID:32939087 PMID:34108479 PMID:34486521 PMID: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 .
PMID:25043379 PMID:30104678 PMID:30321391
Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage .
PMID:32939087
Mediates glutamate and aspartate ADP-ribosylation of target proteins in absence of HPF1 .
PMID:25043379
Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 conferring serine specificity by completing the PARP2 active site .
PMID:28190768 PMID:32028527 PMID:34108479 PMID:34486521 PMID: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 .
PMID:10364231 PMID:32939087 PMID:34108479
HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP2 in order to limit the length of poly-ADP-ribose chains .
PMID:34732825 PMID:34795260
Specifically mediates formation of branched poly-ADP-ribosylation .
PMID:30104678
Branched poly-ADP-ribose chains are specifically recognized by some factors, such as APLF .
PMID: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 PMID:27471034 PMID:29361132
PMID:10364231 PMID:25043379 PMID:27471034 PMID:30104678 PMID:32028527 PMID:32939087 PMID:34108479 PMID:34486521 PMID: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 .
PMID:25043379 PMID:30104678 PMID:30321391
Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage .
PMID:32939087
Mediates glutamate and aspartate ADP-ribosylation of target proteins in absence of HPF1 .
PMID:25043379
Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 conferring serine specificity by completing the PARP2 active site .
PMID:28190768 PMID:32028527 PMID:34108479 PMID:34486521 PMID: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 .
PMID:10364231 PMID:32939087 PMID:34108479
HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP2 in order to limit the length of poly-ADP-ribose chains .
PMID:34732825 PMID:34795260
Specifically mediates formation of branched poly-ADP-ribosylation .
PMID:30104678
Branched poly-ADP-ribose chains are specifically recognized by some factors, such as APLF .
PMID: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 PMID:27471034 PMID:29361132
Protein mono-ADP-ribosyltransferase PARP3
PARP3
inhibitor
Specific functioncatalytic activity
Cellular location
Nucleus
General function & pharmacology
Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins and plays a key role in the response to DNA damage .
PMID:16924674 PMID:19354255 PMID:20064938 PMID:21211721 PMID:21270334 PMID:23742272 PMID:24598253 PMID:25043379 PMID:28447610
Mediates mono-ADP-ribosylation of glutamate, aspartate or lysine residues on target proteins .
PMID:20064938 PMID:25043379
In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation .
PMID: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 .
PMID:16924674 PMID: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 .
PMID:16924674 PMID:21211721 PMID:21270334
Involved in single-strand break repair by catalyzing mono-ADP-ribosylation of histone H2B on 'Glu-2' (H2BE2ADPr) of nucleosomes containing nicked DNA .
PMID:27530147
Cooperates with the XRCC5-XRCC6 (Ku80-Ku70) heterodimer to limit end-resection thereby promoting accurate NHEJ .
PMID:24598253
Suppresses G-quadruplex (G4) structures in response to DNA damage .
PMID:28447610
Associates with a number of DNA repair factors and is involved in the response to exogenous and endogenous DNA strand breaks .
PMID:16924674 PMID:21211721 PMID:21270334
Together with APLF, promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ) .
PMID:21211721
May link the DNA damage surveillance network to the mitotic fidelity checkpoint .
PMID: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 PMID:29361132 PMID:29520010
PMID:16924674 PMID:19354255 PMID:20064938 PMID:21211721 PMID:21270334 PMID:23742272 PMID:24598253 PMID:25043379 PMID:28447610
Mediates mono-ADP-ribosylation of glutamate, aspartate or lysine residues on target proteins .
PMID:20064938 PMID:25043379
In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation .
PMID: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 .
PMID:16924674 PMID: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 .
PMID:16924674 PMID:21211721 PMID:21270334
Involved in single-strand break repair by catalyzing mono-ADP-ribosylation of histone H2B on 'Glu-2' (H2BE2ADPr) of nucleosomes containing nicked DNA .
PMID:27530147
Cooperates with the XRCC5-XRCC6 (Ku80-Ku70) heterodimer to limit end-resection thereby promoting accurate NHEJ .
PMID:24598253
Suppresses G-quadruplex (G4) structures in response to DNA damage .
PMID:28447610
Associates with a number of DNA repair factors and is involved in the response to exogenous and endogenous DNA strand breaks .
PMID:16924674 PMID:21211721 PMID:21270334
Together with APLF, promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ) .
PMID:21211721
May link the DNA damage surveillance network to the mitotic fidelity checkpoint .
PMID: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 PMID:29361132 PMID:29520010
Aldo-keto reductase family 1 member C3
AKR1C3
inhibitor
Specific function15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity
Cellular location
Cytoplasm
General function & pharmacology
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 .
PMID:10622721 PMID:11165022 PMID:7650035 PMID:9415401 PMID: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 .
PMID:11165022 PMID: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 .
PMID:20036328
Reduces prostaglandin (PG) D2 to 11beta-prostaglandin F2, progesterone to 20alpha-hydroxyprogesterone and estrone to 17beta-estradiol .
PMID:10622721 PMID:10998348 PMID:11165022 PMID:15047184 PMID:19010934 PMID: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) .
PMID:10557352 PMID:10998348 PMID:11165022 PMID:14672942 PMID:7650035 PMID:9415401
Also displays retinaldehyde reductase activity toward 9-cis-retinal PMID:21851338
PMID:10622721 PMID:11165022 PMID:7650035 PMID:9415401 PMID: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 .
PMID:11165022 PMID: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 .
PMID:20036328
Reduces prostaglandin (PG) D2 to 11beta-prostaglandin F2, progesterone to 20alpha-hydroxyprogesterone and estrone to 17beta-estradiol .
PMID:10622721 PMID:10998348 PMID:11165022 PMID:15047184 PMID:19010934 PMID: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) .
PMID:10557352 PMID:10998348 PMID:11165022 PMID:14672942 PMID:7650035 PMID:9415401
Also displays retinaldehyde reductase activity toward 9-cis-retinal PMID:21851338
Metabolizing enzymes(4)
Enzymes involved in drug metabolism — important for understanding drug interactions
Enzyme activity key
substrate
inhibitor
inducer
CYP3A4Cytochrome P450 3A4
substrate
inhibitor
CYP3A5Cytochrome P450 3A5
substrate
inhibitor
CYP2B6Cytochrome P450 2B6
inducer
UGT1A1UDP-glucuronosyltransferase 1A1
inhibitor
Transporters(2)
Proteins that transport this drug across cell membranes
ATP-dependent translocase ABCB1
ABCB1
substrate
inhibitor
Specific functionABC-type xenobiotic transporter activity
Cellular location
Cell membrane
General function & pharmacology
Translocates drugs and phospholipids across the membrane .
PMID:2897240 PMID:35970996 PMID:8898203 PMID:9038218 PMID:35507548
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 .
PMID:8898203
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells PMID:2897240 PMID:35970996 PMID:9038218
PMID:2897240 PMID:35970996 PMID:8898203 PMID:9038218 PMID:35507548
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 .
PMID:8898203
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells PMID:2897240 PMID:35970996 PMID:9038218
Broad substrate specificity ATP-binding cassette transporter ABCG2
ABCG2
inhibitor
Specific functionABC-type xenobiotic transporter activity
Cellular location
Cell membrane
General function & pharmacology
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 .
PMID:11306452 PMID:12958161 PMID:19506252 PMID:20705604 PMID:28554189 PMID:30405239 PMID: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 .
PMID:20705604 PMID:23189181
Also mediates the efflux of sphingosine-1-P from cells .
PMID:20110355
Acts as a urate exporter functioning in both renal and extrarenal urate excretion .
PMID:19506252 PMID:20368174 PMID:22132962 PMID:31003562 PMID: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 .
PMID:12682043 PMID:28554189 PMID: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 .
PMID:11306452 PMID:12477054 PMID:15670731 PMID:18056989 PMID: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).
In inflammatory macrophages, exports itaconate from the cytosol to the extracellular compartment and limits the activation of TFEB-dependent lysosome biogenesis involved in antibacterial innate immune response
PMID:11306452 PMID:12958161 PMID:19506252 PMID:20705604 PMID:28554189 PMID:30405239 PMID: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 .
PMID:20705604 PMID:23189181
Also mediates the efflux of sphingosine-1-P from cells .
PMID:20110355
Acts as a urate exporter functioning in both renal and extrarenal urate excretion .
PMID:19506252 PMID:20368174 PMID:22132962 PMID:31003562 PMID: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 .
PMID:12682043 PMID:28554189 PMID: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 .
PMID:11306452 PMID:12477054 PMID:15670731 PMID:18056989 PMID: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).
In inflammatory macrophages, exports itaconate from the cytosol to the extracellular compartment and limits the activation of TFEB-dependent lysosome biogenesis involved in antibacterial innate immune response
Carriers(2)
Proteins that carry this drug through the body
Albumin
ALB
binder
Specific functionantioxidant activity
Cellular location
Secreted
General function & pharmacology
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 .
PMID: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 .
PMID:6234017
Does not prevent iron uptake by the bacterial siderophore aerobactin PMID:6234017
PMID: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 .
PMID:6234017
Does not prevent iron uptake by the bacterial siderophore aerobactin PMID:6234017
Alpha-1-acid glycoprotein 1
ORM1
binder
Cellular location
Secreted
General function & pharmacology
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
Appears to function in modulating the activity of the immune system during the acute-phase reaction
Scientific references(6)
Solimando DA Jr, Waddell J.A.
Nivolumab and Olaparib.
Hosp Pharmacy
2015 May50(5):356-66. doi: 10.1310/hpj5005-356
Bochum S., Berger S., Martens U.M.
Olaparib.
Recent Results Cancer Research
2018211:217-233. doi: 10.1007/978-3-319-91442-8_15
Wang L., Wang M.
In vitro metabolism of olaparib in liver microsomes by liquid chromatography/electrospray ionization high-resolution mass spectrometry.
Rapid Communications Mass Spectrom
2020 Feb 1534(3):e8575. doi: 10.1002/rcm.8575
Sachdev E., Tabatabai R., Roy V., Rimel B.J., Mita M.M.
PARP Inhibition in Cancer: An Update on Clinical Development.
Target Oncology
2019 Dec14(6):657-679. doi: 10.1007/s11523-019-00680-2
Deeks E.D.
Olaparib: first global approval.
Drugs
2015 Feb75(2):231-40. doi: 10.1007/s40265-015-0345-6
Chen Y., Zhang L., Hao Q.
Olaparib: a promising PARP inhibitor in ovarian cancer therapy.
Arch Gynecology Obstetrics
2013 Aug288(2):367-74. doi: 10.1007/s00404-013-2856-2. Epub 2013 Apr 26
ATC classification(1 code)
ATC L01XK01
Affected organisms(1)
Humans and other mammals
Experimental properties(1)
Commercial products(13)
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Show
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Linked compound data from DrugBank Open Data (CC BY-NC 4.0)
Olaparib
Additional database identifiers
Drugs Product Database (DPD)
22712
ChemSpider
23343272
BindingDB
27566
PDB
09L
ZINC
ZINC000040430143
HUGO Gene Nomenclature Committee (HGNC)
HGNC:270
GenAtlas
PARP1
GeneCards
PARP1
GenBank Gene Database
X16674
GenBank Protein Database
1017423
Guide to Pharmacology
2771
UniProt Accession
PARP1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:272
GeneCards
PARP2
GenBank Gene Database
AJ236912
GenBank Protein Database
6688130
Guide to Pharmacology
2772
UniProt Accession
PARP2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:273
GeneCards
PARP3
GenBank Gene Database
Y16836
GenBank Protein Database
29788060
Guide to Pharmacology
2864
UniProt Accession
PARP3_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:386
GenAtlas
AKR1C3
GeneCards
AKR1C3
GenBank Gene Database
S68288
GenBank Protein Database
4261711
Guide to Pharmacology
1382
UniProt Accession
AK1C3_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2637
GenAtlas
CYP3A4
GeneCards
CYP3A4
GenBank Gene Database
M18907
Guide to Pharmacology
1337
UniProt Accession
CP3A4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2638
GenAtlas
CYP3A5
GeneCards
CYP3A5
GenBank Gene Database
J04813
GenBank Protein Database
181346
Guide to Pharmacology
1338
UniProt Accession
CP3A5_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2615
GeneCards
CYP2B6
GenBank Gene Database
M29874
GenBank Protein Database
181296
Guide to Pharmacology
1324
UniProt Accession
CP2B6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12530
GeneCards
UGT1A1
GenBank Gene Database
M57899
GenBank Protein Database
184473
Guide to Pharmacology
2990
UniProt Accession
UD11_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:399
GenAtlas
ALB
GeneCards
ALB
GenBank Gene Database
V00494
GenBank Protein Database
28590
UniProt Accession
ALBU_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8498
GenAtlas
ORM1
GeneCards
ORM1
GenBank Gene Database
X02544
GenBank Protein Database
757907
UniProt Accession
A1AG1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:40
GenAtlas
ABCB1
GeneCards
ABCB1
GenBank Gene Database
M14758
GenBank Protein Database
307180
Guide to Pharmacology
768
UniProt Accession
MDR1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:74
GenAtlas
ABCG2
GeneCards
ABCG2
GenBank Gene Database
AF103796
GenBank Protein Database
4185796
Guide to Pharmacology
792
UniProt Accession
ABCG2_HUMAN
Patent information
11 active patents, 6 expired
11970530
United States
Approved 30 Apr 2024 · Expires 25 Oct 2041
15y 6m
8859562
United States
Approved 14 Oct 2014 · Expires 4 Aug 2031
5y 4m
8475842
United States
Approved 2 Jul 2013 · Expires 31 Dec 2029
3y 9m
11633396
United States
Approved 25 Apr 2023 · Expires 7 Oct 2029
3y 6m
11975001
United States
Approved 7 May 2024 · Expires 7 Oct 2029
3y 6m
The earliest active patent expires August 2027. Generic versions may become available after this date.
Source: DrugBank · CC BY-NC 4.0. Patent data sourced from national patent offices. Expiry dates may not reflect extensions, regulatory exclusivity periods, or legal challenges.
DrugBank citations
If you use DrugBank data in your research, please cite the following publications:
Knox C., Wilson M., Klinger C.M., et al
DrugBank 6.
0: the DrugBank Knowledgebase for 2024
Nucleic Acids Res. 2024 Jan 552(D1):D1265-D1275
Wishart D.S., Feunang Y.D., Guo A.C., et al
DrugBank 5.
0: a major update to the DrugBank database for 2018
Nucleic Acids Res. 2017 Nov 846(D1):D1074-D1082
Show earlier publications
Law V., Knox C., Djoumbou Y., et al
DrugBank 4.
0: shedding new light on drug metabolism
Nucleic Acids Res. 2014 Jan 142(1):D1091-7
Knox C., Law V., Jewison T., et al
DrugBank 3.
0: a comprehensive resource for 'omics' research on drugs
Nucleic Acids Res. 2011 Jan39(Database issue):D1035-41
Wishart D.S., Knox C., Guo A.C., et al
DrugBank: a knowledgebase for drugs, drug actions and drug targets.
Nucleic Acids Research
2008 Jan36(Database issue):D901-6
Wishart D.S., Knox C., Guo A.C., et al
DrugBank: a comprehensive resource for in silico drug discovery and exploration.
Nucleic Acids Research
2006 Jan 134(Database issue):D668-72
Source: go.drugbank.comCC BY-NC 4.0
Updated about 1 month ago(4 Mar 2026)