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Details

Stereochemistry ABSOLUTE
Molecular Formula C19H20N4O
Molecular Weight 320.3883
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NIRAPARIB

SMILES

NC(=O)C1=CC=CC2=CN(N=C12)C3=CC=C(C=C3)[C@@H]4CCCNC4

InChI

InChIKey=PCHKPVIQAHNQLW-CQSZACIVSA-N
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

HIDE SMILES / InChI

Description

Niraparib (MK-4827) displays excellent PARP 1 and 2 inhibition. Inhibition of PARP in the context of defects in other DNA repair mechanisms provide a tumor specific way to kill cancer cells. Niraparib is in development with TESARO, under licence from Merck & Co, for the treatment of cancers (ovarian, fallopian tube and peritoneal cancer, breast cancer, prostate cancer and Ewing's sarcoma). Niraparib was characterized in a number of preclinical models before moving to phase I clinical trials, where it showed excellent human pharmacokinetics suitable for once a day oral dosing, achieved its pharmacodynamic target for PARP inhibition, and had promising activity in cancer patients. It is currently being tested in phase 3 clinical trials as maintenance therapy in ovarian cancer and as a treatment for breast cancer.

CNS Activity

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
Patents

Sample Use Guides

In Vivo Use Guide
Niraparib (PO, 110-210 mg) successfully inhibited poly(ADP-ribose) polymerase (PARP) during a phase I trial in patients with BRCA-deficient or sporadic cancers associated with homologous recombination repair defects. Niraparib (PO, 30-210 mg) was well tolerated during a phase I trial in patients with BRCA-deficient or sporadic cancers associated with homologous recombination repair defects. Maximum tolerated dose (MTD) of niraparib in patients with advanced solid tumours was 300 mg.
Route of Administration: Oral
In Vitro Use Guide
Niraparib (MK-4827) inhibited proliferation of cancer cells with mutant BRCA-1 and BRCA-2 with CC(50) in the 10-100 nM range.
Name Type Language
NIRAPARIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
MK-4827
Code English
2-(4-((3S)-PIPERIDIN-3-YL)PHENYL)-2H-INDAZOLE-7-CARBOXAMIDE
Systematic Name English
NIRAPARIB [WHO-DD]
Common Name English
NIRAPARIB [USAN]
Common Name English
2H-INDAZOLE-7-CARBOXAMIDE, 2-(4-(3S)-3-PIPERIDINYLPHENYL)-
Systematic Name English
MK4827
Code English
NIRAPARIB [INN]
Common Name English
Code System Code Type Description
EPA CompTox
1038915-60-4
Created by admin on Tue Mar 06 11:10:27 UTC 2018 , Edited by admin on Tue Mar 06 11:10:27 UTC 2018
PRIMARY
NCI_THESAURUS
C80059
Created by admin on Tue Mar 06 11:10:27 UTC 2018 , Edited by admin on Tue Mar 06 11:10:27 UTC 2018
PRIMARY
WIKIPEDIA
NIRAPARIB
Created by admin on Tue Mar 06 11:10:27 UTC 2018 , Edited by admin on Tue Mar 06 11:10:27 UTC 2018
PRIMARY
PUBCHEM
24958200
Created by admin on Tue Mar 06 11:10:27 UTC 2018 , Edited by admin on Tue Mar 06 11:10:27 UTC 2018
PRIMARY SWITZERF
ChEMBL
CHEMBL1094636
Created by admin on Tue Mar 06 11:10:27 UTC 2018 , Edited by admin on Tue Mar 06 11:10:27 UTC 2018
PRIMARY
CAS
1038915-60-4
Created by admin on Tue Mar 06 11:10:27 UTC 2018 , Edited by admin on Tue Mar 06 11:10:27 UTC 2018
PRIMARY
RXCUI
1918231
Created by admin on Tue Mar 06 11:10:27 UTC 2018 , Edited by admin on Tue Mar 06 11:10:27 UTC 2018
PRIMARY
EVMPD
SUB177208
Created by admin on Tue Mar 06 11:10:27 UTC 2018 , Edited by admin on Tue Mar 06 11:10:27 UTC 2018
PRIMARY
INN
9526
Created by admin on Tue Mar 06 11:10:27 UTC 2018 , Edited by admin on Tue Mar 06 11:10:27 UTC 2018
PRIMARY