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Niraparib (MK-4827)

Name: Niraparib (MK-4827)
Brand: Selleck Chemicals
SKU: S2741
Rating: 5 (102 reviews)

Catalog No.S2741 Purity:99.99%

Niraparib (MK-4827) is a selective inhibitor of PARP1/2 with IC50 of 3.8 nM/2.1 nM, with great activity in cancer cells with mutant BRCA-1 and BRCA-2. It is >330-fold selective against PARP3, V-PARP and Tank1. Niraparib can form PARP–DNA complexes resulting in DNA damage, apoptosis, and cell death. Phase 3.

Niraparib (MK-4827) Chemical Structure

CAS No. 1038915-60-4

Purity & Quality Control

Batch: Purity: 99.99%

99.99

Niraparib (MK-4827) Related Products

Related Targets	PARP1 PARP2 PARP3 Tankyrase-1 Tankyrase-2 PARP14 PARP7 TNKS1 TNKS2	Click to Expand
Related Products	XAV-939 Veliparib (ABT-888) PJ34 HCl AG-14361 Iniparib (BSI-201) A-966492 G007-LK UPF 1069 AZD2461 Pamiparib ME0328 3-Aminobenzamide NMS-P118 Stenoparib (E7449) NVP-TNKS656 WIKI4 Benzamide BGP-15 2HCl NU1025 BYK204165 Fluzoparib (SHR-3162) Picolinamide	Click to Expand
Related Compound Libraries	FDA-approved Drug Library Natural Product Library Apoptosis Compound Library DNA Damage/DNA Repair compound Library Cell Cycle compound library	Click to Expand

Signaling Pathway

PARP Signaling Pathway

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
HeLa cells	Function assay			Inhibition of PARP in hydrogen peroxide-induced human HeLa cells assessed as inhibition DNA-damage-induced PARylation, EC50=0.004 μM	19873981
A549 cells	Cytotoxicity assay		5-7 days	Cytotoxicity against human A549 cells transfected with BRCA2 shRNA assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50=0.011 μM	25761096
MDA-MB-436 cells	Proliferation assay		6 days	Antiproliferative activity against human MDA-MB-436 cells expressing BRCA1 5396 + 1G>A mutant after 6 days by cell titer-blue assay, CC50=18 nM	19873981
SUM1315MO2 cells	Cytotoxicity assay		12 days	Cytotoxicity against human SUM1315MO2 cells carrying BRCA1 mutant assessed as inhibition of cell proliferation after 12 days by CellTiter-Blue assay, CC50=0.02 μM	25761096
DoTc2-4510 cells	Cytotoxicity assay		5-7 days	Cytotoxicity against human DoTc2-4510 cells carrying BRCA2 mutant assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50=0.023 μM	25761096
SUM149PT cells	Cytotoxicity assay		5-7 days	Cytotoxicity against human SUM149PT cells carrying BRCA1 mutant assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50=0.024 μM	25761096
UWB1.289 cells	Cytotoxicity assay		5-7 days	Cytotoxicity against human UWB1.289 cells carrying BRCA1 mutant assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50=0.056 μM	25761096
Capan1 cells	Cytotoxicity assay			Cytotoxicity against BRCA2-deficient human Capan1 cells, CC50=0.09 μM	25761096
Jurkat cells	Function assay			Inhibition of PARP1 in human Jurkat cells assessed as reduction of cell viability after 96 hrs by MTS assay in presence of 100 uM of temozolomide, EC50=0.2 μM	23850199
BT20 cells	Cytotoxicity assay		5-7 days	Cytotoxicity against human BT20 cells assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50=2.2 μM	25761096
Antiproliferative assay	HeLa		7 days	Antiproliferative activity against BRCA1 deficient human HeLa cells after 7 days by cell titer-blue assay, CC50 = 0.033 μM.	19873981
Function assay	HeLa			Inhibition of PARP in hydrogen peroxide-induced human HeLa cells assessed as inhibition DNA-damage-induced PARylation, EC90 = 0.045 μM.	19873981
Antiproliferative assay	Capan1		13 days	Antiproliferative activity against human Capan1 cells expressing BRCA2 6174delT mutation and loss of wild-type allele after 13 days by cell titer-blue assay, CC50 = 0.09 μM.	19873981
Antiproliferative assay	HeLa		7 days	Antiproliferative activity against human HeLa cells expressing wild type BRCA1 after 7 days by cell titer-blue assay, CC50 = 0.86 μM.	19873981
Function assay	Jurkat		96 hrs	Inhibition of PARP1 in human Jurkat cells assessed as reduction of cell viability after 96 hrs by MTS assay, EC50 = 31 μM.	23850199
Function assay	CAPAN-1			Inhibition of PARP in BRCA2-deficient human CAPAN-1 cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, IC50 = 0.0035 μM.	25761096
Function assay	HeLa			Inhibition of PARP in human HeLa cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, EC50 = 0.004 μM.	25761096
Function assay	A2780			Inhibition of PARP in human A2780 cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, IC50 = 0.004 μM.	25761096
Cytotoxicity assay	MDA-MB-436			Cytotoxicity against human MDA-MB-436 cells carrying BRCA1 mutant assessed as inhibition of cell proliferation, CC50 = 0.018 μM.	25761096
Cytotoxicity assay	HeLa		5 to 7 days	Cytotoxicity against human HeLa cells transfected with BRCA1 shRNA assessed as reduction of cell viability after 5 to 7 days by CellTiter-Blue assay, CC50 = 0.034 μM.	25761096
Function assay	HeLa			Inhibition of PARP in human HeLa cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, IC90 = 0.046 μM.	25761096
Function assay	CAPAN-1			Inhibition of PARP in BRCA2-deficient human CAPAN-1 cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, IC90 = 0.05 μM.	25761096
Function assay	A2780			Inhibition of PARP in human A2780 cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, IC90 = 0.052 μM.	25761096
Cytotoxicity assay	HeLa		5 to 7 days	Cytotoxicity against wild type human HeLa cells assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50 = 0.852 μM.	25761096
Cytotoxicity assay	UWB1.289		5 to 7 days	Cytotoxicity against human UWB1.289 cells expressing BRCA1 assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50 = 0.975 μM.	25761096
Cytotoxicity assay	A549		5 to 7 days	Cytotoxicity against wild type human A549 cells assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50 = 1.76 μM.	25761096
Cytotoxicity assay	Capan1			Cytotoxicity against BRCA2-deficient human Capan1 cells, EC50 = 0.65 μM.	26652717
Antitumor assay	MDA-MB-436	50 mg/kg	33 days	Antitumor activity against human MDA-MB-436 cells expressing BRCA1 5396 + 1G>A mutant xenografted in CD1 mouse assessed as tumor regression at 50 mg/kg, po bid for 33 days	19873981
Antitumor assay	MDA-MB-436	100 mg/kg	33 days	Antitumor activity against human MDA-MB-436 cells expressing BRCA1 5396 + 1G>A mutant xenografted in CD1 mouse assessed as tumor regression at 100 mg/kg, po qd for 33 days	19873981
Antitumor assay	MDA-MB-436	80 mg/kg	1 to 2 weeks	Antitumor activity against human MDA-MB-436 cells harboring BRCA1 mutant xenografted in immunocompromised mouse assessed as tumor growth inhibition at 80 mg/kg, po qd for 1 to 2 weeks	25761096
Antitumor assay	MDA-MB-436	80 mg/kg	4 weeks	Antitumor activity against human MDA-MB-436 cells harboring BRCA1 mutant xenografted in immunocompromised mouse assessed as complete and sustained tumor regression at 80 mg/kg, po qd for 4 weeks	25761096
Antitumor assay	MDA-MB-436	50 mg/kg		Antitumor activity against human MDA-MB-436 cells harboring BRCA1 mutant xenografted in immunocompromised mouse assessed as tumor growth inhibition at 50 mg/kg, po administered daily	25761096
Antitumor assay	MDA-MB-436	80 mg/kg	3 weeks	Antitumor activity against human MDA-MB-436 cells harboring BRCA1 mutant xenografted in immunocompromised mouse assessed as tumor shrinkage at 80 mg/kg, po qd for 3 weeks	25761096
qHTS assay	TC32			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
qHTS assay	A673			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
qHTS assay	NB1643			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
qHTS assay	A673			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
qHTS assay	BT-37			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells	29435139
qHTS assay	SK-N-MC			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
qHTS assay	NB-EBc1			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
qHTS assay	LAN-5			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
qHTS assay	SK-N-MC			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
qHTS assay	TC32			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
Click to View More Cell Line Experimental Data

Biological Activity

Description

Targets

PARP2 ^[1] (Cell-free assay)	PARP1 ^[1] (Cell-free assay)
2.1 nM	3.8 nM

In vitro
In vitro	In a whole cell assay, MK-4827 inhibited PARP activity with EC50 = 4 nM and inhibited proliferation of cancer cells with mutant BRCA-1 and BRCA-2 with CC50 in the 10-100 nM range. It was demonstrated to be a potent and selective PARP-1 and PARP-2 inhibitor with IC50=3.8 and 2.1 nM, respectively. Furthermore, it displayed at least a 100-fold selectivity over PARP-3, V-PARP, and tankyrase-1, with IC50 = 1300, 330, and 570 nM, respectively. As well as inhibiting the growth of HeLa cell lacking BRCA-1 because of silencing by RNA interference, MK-4827 is able to inhibit the proliferation of cancer cell lines carrying natural BRCA-1 or BRCA-2 mutations. In MDA-MB-436 human mammary gland adenocarcinoma cells carrying BRCA-1 mutations, MK-4827 displayed CC50 = 18 nM, while in CAPAN-1 human pancreatic adenocarcinoma cells, which are BRCA-2 mutant, MK-4827 displayed CC50 = 90 nM. In contrast, normal human prostate and mammary epithelial cells are resistant to MK-4827, displaying antiproliferative effects in the micromolar range, thereby demonstrating the very high selective cytotoxicity from these PARP inhibitors in BRCA-1 and -2 mutant cancer cells compared to surrounding tissue^[2].
Cell Research	Cell lines	HeLa BRCA1-silenced cells
	Concentrations	serial dilutions
	Incubation Time	7 days
	Method	Proliferation assays were conducted in 96-well black viewplates, and 300 cells/well (250 cell/well for BRCA-1 wt) in culture medium, 190 μL/well (DMEM containing 10% FCS, 0.1 mg/mL penicillin-streptomycin, and 2 mM L-glutamine), were plated and incubated for 4 h at 37℃ under 5% CO2 atmosphere. Inhibitors were then added with serial dilutions, 10 μL/well to obtain the desired final compound concentration in 0.5% DMSO. The cells were then incubated for 7 days at 37℃ in 5% CO2 after which time viability was assessed. Briefly, with CellTiter-Blue solution prediluted 1:10 in medium, 100 μL/well was added and the cells left for 45 min at 37℃ under 5% CO2 and then a further 15 min at room temperature in the dark. The number of living cells was determined by reading the plate at fluorimeter, excitation at 550 nm and emission at 590 nm. Cell growth was expressed as the percentage growth with respect to vehicle treated cells. The concentration required to inhibit cell growth by 50% (CC50) was determined.
Experimental Result Images	Methods	Biomarkers	Images	PMID
	Western blot	c-PARP /c-caspase 3 / γ-H2AX		29158830
	Immunofluorescence	Rad51 / Geminin		27614696

In Vivo
In vivo	MK-4827, a novel, orally bioavailable, PARP-1 and PARP-2 inhibitor, strongly enhanced the effect of radiation on a variety of human tumor xenografts, both p53 wild type and p53 mutant^[1]. It was well tolerated in vivo and demonstrated efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer^[2].
Animal Research	Animal Models	Female nude mice
	Dosages	25 mg/kg twice daily or 50 mg/kg once daily
	Administration	oral administration

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT05289648	Not yet recruiting	Endometrial Cancer\|Serous Adenocarcinoma\|Uterine Neoplasm	Sir Mortimer B. Davis - Jewish General Hospital	May 1 2024	Early Phase 1
NCT06077877	Recruiting	Neoplasms	GlaxoSmithKline	October 24 2023	Phase 1\|Phase 2
NCT05666349	Withdrawn	Recurrent Glioblastoma	University College London\|GlaxoSmithKline	October 13 2023	Phase 1

References

Chemical Information & Solubility

Molecular Weight	320.39	Formula	C₁₉H₂₀N₄O
CAS No.	1038915-60-4	SDF	Download Niraparib (MK-4827) SDF
Smiles	C1CC(CNC1)C2=CC=C(C=C2)N3C=C4C=CC=C(C4=N3)C(=O)N
Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 64 mg/mL ( (199.75 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 64 mg/mL

Water : Insoluble

Molecular Weight Calculator

In vivo Batch: Add solvents to the product individually and in order.				In vivo Formulation Calculator
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	2.500mg/ml (7.80mM)	Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	2.500mg/ml (7.80mM)	Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Preparing Stock Solutions

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
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Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
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Frequently Asked Questions

Question 1:
How to reconstitute the compound for in vivo studies?

Answer:
You can use the formulation 1% CMC-Na (suspension) for oral administration.

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