niraparib   Click here for help

GtoPdb Ligand ID: 8275

Synonyms: Akeega® (niraparib and abiraterone acetate) | compound 56 [PMID 19873981] | MK 4827 | MK-4827 | Zejula®
Approved drug PDB Ligand
niraparib is an approved drug (EMA & FDA (2017))
Compound class: Synthetic organic
Comment: Niraparib is a novel orally available poly(ADP-ribose) polymerase (PARP) inhibitor [4].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 3
Topological polar surface area 72.42
Molecular weight 320.16
XLogP 2.76
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES NC(=O)c1cccc2c1nn(c2)c1ccc(cc1)C1CCCNC1
Isomeric SMILES NC(=O)c1cccc2c1nn(c2)c1ccc(cc1)[C@@H]1CCCNC1
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
InChI Key PCHKPVIQAHNQLW-CQSZACIVSA-N
No information available.
Summary of Clinical Use Click here for help
The FDA granted niraparib orphan drug designation for the treatment of ovarian cancer [6]. This was converted to full approval in March 2017, for the treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in a complete or partial response to platinum-based chemotherapy. This drug is administered orally, once-daily.
Phase 3 clinical trial in HER2 -ve/BRCA mutation +ve breast cancer (NCT01905592) is ongoing. In April 2020, the FDA expanded use of niraparib as a maintenance treatment for patients with the initial indicated cancer settings.
In August 2023 the FDA approved Akeega®, first-in-class dual action tablet that contains niraparib plus the androgen synthesis inhibitor abiraterone acetate, for the treatment of metastatic castration-resistant prostate cancer (mCRPC) with a confirmed BRCA mutation.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
PARP inhibitors may funtion by trapping PARPs on DNA [5], generating cytotoxic PARP-DNA complexes. PARP inhibition is particularly toxic in cancer cell lines [1-2]and human tumours [3] that lack the DNA repair mechanism of BRCA1 or BRCA2 ..
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01905592 A Phase III Trial of Niraparib Versus Physician's Choice in HER2 Negative, Germline BRCA Mutation-positive Breast Cancer Patients Phase 3 Interventional Tesaro, Inc.
External links Click here for help
For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com
European Medicines Agency (EMA)