Identification
- Summary
Niraparib is a poly-ADP ribose polymerase inhibitor used to treat recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer responding to platinum based chemotherapy.
- Brand Names
- Zejula
- Generic Name
- Niraparib
- DrugBank Accession Number
- DB11793
- Background
Niraparib is an orally active PARP inhibitor developed by Tesaro to treat ovarian cancer. FDA approval on March 2017.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 320.396
Monoisotopic: 320.16371128 - Chemical Formula
- C19H20N4O
- Synonyms
- Niraparib
- External IDs
- MK 4827
- MK-4827
- MK-4827 FREE BASE
- MK4827
Pharmacology
- Indication
Niraparib 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
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- Associated Therapies
- Contraindications & Blackbox Warnings
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- Pharmacodynamics
Cardiovascular Effects: Niraparib has the potential to cause effects on pulse rate and blood pressure in patients receiving the recommended dose, which may be related to pharmacological inhibition of the dopamine transporter (DAT), norepinephrine transporter (NET) and serotonin transporter (SERT). In the NOVA study, mean pulse rate and blood pressure increased over baseline in the niraparib arm relative to the placebo arm at all on-study assessments. Mean greatest increases from baseline in pulse rate on treatment were 24.1 and 15.8 beats/min in the niraparib and placebo arms, respectively. Mean greatest increases from baseline in systolic blood pressure on treatment were 24.5 and 18.3 mmHg in the niraparib and placebo arms, respectively. Mean greatest increases from baseline in diastolic blood pressure on treatment were 16.5 and 11.6 mmHg in the niraparib and placebo arms, respectively.
Cardiac Electrophysiology The potential for QTc prolongation with niraparib was evaluated in a randomized, placebo-controlled trial in cancer patients (367 patients on niraparib and 179 patients on placebo). No large changes in the mean QTc interval (>20 ms) were detected in the trial following the treatment of niraparib 300 mg once daily.- Mechanism of action
Niraparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, PARP-1 and PARP-2, which play a role in DNA repair. In vitro studies have shown that niraparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis and cell death. Increased niraparib-induced cytotoxicity was observed in tumor cell lines with or without deficiencies in BRCA1/2. Niraparib decreased tumor growth in mouse xenograft models of human cancer cell lines with deficiencies in BRCA1/2 and in human patient-derived xenograft tumor models with homologous recombination deficiency that had either mutated or wild type BRCA1/2.
Target Actions Organism APoly [ADP-ribose] polymerase 1 antagonistHumans APoly [ADP-ribose] polymerase 2 antagonistHumans - Absorption
The absolute bioavailability of niraparib is approximately 73%. Following oral administration of niraparib, peak plasma concentration, Cmax, is reached within 3 hours. Concomitant administration of a high fat meal (800-1,000 calories with approximately 50% of total caloric content of the meal from fat) did not significantly affect the pharmacokinetics of niraparib.
Following a single-dose administration of 300 mg niraparib, the mean (±SD) peak plasma concentration (Cmax) was 804 (± 403) ng/mL. The systemic exposures (Cmax and AUC) of niraparib increased in a dose proportional manner with daily doses ranging 30 mg (0.1 times the approved recommended dosage) to 400 mg (1.3 times the approved recommended dosage). The accumulation ratio of niraparib exposure following 21 days of repeated daily doses was approximately 2 fold for doses ranging from 30 mg to 400 mg.- Volume of distribution
The average (±SD) apparent volume of distribution (Vd/F) was 1220 (±1114) L.
- Protein binding
Niraparib is 83.0% bound to human plasma proteins.
- Metabolism
Niraparib is metabolized primarily by carboxylesterases (CEs) to form a major inactive metabolite, which subsequently undergoes glucuronidation.
- Route of elimination
Following administration of a single oral 300 mg dose of radio-labeled niraparib, the average percent recovery of the administered dose over 21 days was 47.5% (range 33.4% to 60.2%) in urine, and 38.8% (range 28.3% to 47.0%) in feces.
- Half-life
Following multiple daily doses of 300 mg niraparib, the mean half-life (t1/2) is 36 hours.
- Clearance
the apparent total clearance (CL/F) of niraparib was 16.2 L/h in cancer patients.
- Adverse Effects
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- Toxicity
Not Available
- 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 softwareDarbepoetin alfa The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Niraparib. Erythropoietin The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Niraparib. Methoxy polyethylene glycol-epoetin beta The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Niraparib. Peginesatide The risk or severity of Thrombosis can be increased when Peginesatide is combined with Niraparib. Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - Food Interactions
- Take at the same time every day.
- Take with or without food.
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.
- Product Ingredients
Ingredient UNII CAS InChI Key Niraparib hydrochloride L4JFC1PHCI 1038915-64-8 YXYDNYFWAFBCAN-PFEQFJNWSA-N Niraparib tosylate 75KE12AY9U 1038915-73-9 LCPFHXWLJMNKNC-PFEQFJNWSA-N Niraparib tosylate monohydrate 195Q483UZD 1613220-15-7 ACNPUCQQZDAPJH-FMOMHUKBSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Zejula Capsule 100 mg Oral Glaxo Smith Kline (Ireland) Limited 2020-12-16 Not applicable EU Zejula Capsule 100 mg Oral Glaxo Smith Kline (Ireland) Limited 2020-12-16 Not applicable EU Zejula Capsule 100 mg Oral Glaxosmithkline Inc 2020-01-09 Not applicable Canada Zejula Capsule 100 mg Oral Glaxo Smith Kline (Ireland) Limited 2020-12-16 Not applicable EU Zejula Capsule 100 mg/1 Oral GlaxoSmithKline LLC 2017-03-27 Not applicable US
Categories
- ATC Codes
- L01XX54 — Niraparib
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylpiperidines. These are compounds containing a phenylpiperidine skeleton, which consists of a piperidine bound to a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Piperidines
- Sub Class
- Phenylpiperidines
- Direct Parent
- Phenylpiperidines
- Alternative Parents
- Phenylpyrazoles / Indazoles / Aralkylamines / Benzene and substituted derivatives / Heteroaromatic compounds / Primary carboxylic acid amides / Amino acids and derivatives / Dialkylamines / Azacyclic compounds / Organooxygen compounds show 2 more
- Substituents
- Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenoid / Benzopyrazole / Carboxamide group / Carboxylic acid derivative show 15 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- HMC2H89N35
- CAS number
- 1038915-60-4
- InChI Key
- PCHKPVIQAHNQLW-CQSZACIVSA-N
- InChI
- InChI=1S/C19H20N4O/c20-19(24)17-5-1-3-15-12-23(22-18(15)17)16-8-6-13(7-9-16)14-4-2-10-21-11-14/h1,3,5-9,12,14,21H,2,4,10-11H2,(H2,20,24)/t14-/m1/s1
- IUPAC Name
- 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide
- SMILES
- NC(=O)C1=CC=CC2=CN(N=C12)C1=CC=C(C=C1)[C@@H]1CCCNC1
References
- General References
- External Links
- PubChem Compound
- 24958200
- PubChem Substance
- 347828142
- ChemSpider
- 24531930
- BindingDB
- 50316226
- 1918231
- ChEMBL
- CHEMBL1094636
- ZINC
- ZINC000043206370
- PharmGKB
- PA166131610
- PDBe Ligand
- 3JD
- Wikipedia
- Niraparib
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Ovarian Cancer 1 4 Not Yet Recruiting Treatment Advanced Ovarian Cancer / Epithelial Ovarian Cancer / Ovarian Cancer / Stage III Ovarian Cancer 1 4 Recruiting Prevention Adult Patients With Platinum-sensitive, Relapsed, High Grade Serous Epithelial Ovarian Cancer 1 3 Active Not Recruiting Treatment Castration Resistant Prostatic Cancer 1 3 Active Not Recruiting Treatment Neoplasms, Ovarian 1 3 Active Not Recruiting Treatment Neoplasms, Ovarian / Ovarian Cancer 1 3 Active Not Recruiting Treatment Neoplastic Disease 1 3 Active Not Recruiting Treatment Recurrent Ovarian Carcinoma 1 3 Completed Treatment BRCA 1 Gene Mutation / BRCA 2 Gene Mutation / Breast Carcinoma / Human Epidermal Growth Factor 2 Negative Carcinoma of Breast / Neoplasms, Breast / Neoplasms, Ovarian 1 3 Completed Treatment Neoplasms, Ovarian / Platinum Sensitive Ovarian Cancer 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 100 mg Capsule Oral 100 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8859562 No 2014-10-14 2031-08-04 US US8143241 No 2012-03-27 2027-08-12 US US8071579 No 2011-12-06 2027-08-12 US US8071623 No 2011-12-06 2030-03-22 US US8436185 No 2013-05-07 2029-04-24 US US11091459 No 2021-08-17 2038-03-27 US
Properties
- State
- Not Available
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0149 mg/mL ALOGPS logP 2.45 ALOGPS logP 2.47 ChemAxon logS -4.3 ALOGPS pKa (Strongest Acidic) 14.03 ChemAxon pKa (Strongest Basic) 10.1 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 3 ChemAxon Hydrogen Donor Count 2 ChemAxon Polar Surface Area 72.94 Å2 ChemAxon Rotatable Bond Count 3 ChemAxon Refractivity 94.92 m3·mol-1 ChemAxon Polarizability 36.41 Å3 ChemAxon Number of Rings 4 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 Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets

- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Zinc ion binding
- Specific Function
- Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This ...
- Gene Name
- PARP1
- Uniprot ID
- P09874
- Uniprot Name
- Poly [ADP-ribose] polymerase 1
- Molecular Weight
- 113082.945 Da
References
- PARP inhibitor, MK-4827, shows anti-tumor activity in first trial in humans [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Nad+ adp-ribosyltransferase activity
- Specific Function
- Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This ...
- Gene Name
- PARP2
- Uniprot ID
- Q9UGN5
- Uniprot Name
- Poly [ADP-ribose] polymerase 2
- Molecular Weight
- 66205.31 Da
References
- PARP inhibitor, MK-4827, shows anti-tumor activity in first trial in humans [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Carboxylic ester hydrolase activity
- Specific Function
- Not Available
- Gene Name
- CES1A1a
- Uniprot ID
- Q6LAP9
- Uniprot Name
- Carboxylesterase
- Molecular Weight
- 1908.25 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Receptor binding
- Specific Function
- Plays an important role in the degradation of dermatan and keratan sulfates.
- Gene Name
- GUSB
- Uniprot ID
- P08236
- Uniprot Name
- Beta-glucuronidase
- Molecular Weight
- 74731.46 Da
Drug created at October 20, 2016 20:48 / Updated at June 28, 2022 06:16