Niraparib (MK-4827)

Catalog No.S2741

Molecular Weight(MW): 320.39

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. Phase 3.

Cited by 13 Publications

Nat Med, 2019, 25(5):838-849

PubMed: 31011202 ( click the link to review the publication )

Cancer Discov, 2019, 9(7):852-871

PubMed: 31053628 ( click the link to review the publication )

Cell, 2018, 172(1-2):373-386

PubMed: 29224780 ( click the link to review the publication )

Cell Rep, 2019, 27(12):3422-3432

PubMed: 31216465 ( click the link to review the publication )

Biochem Biophys Res Commun, 2019, 510(4):501-507

PubMed: 30737031 ( click the link to review the publication )

Spectrochim Acta A Mol Biomol Spectrosc, 2019, 206:126-134

PubMed: 30096696 ( click the link to review the publication )

Nat Commun, 2018, 9(1):2678

PubMed: 29992957 ( click the link to review the publication )

Cancer Biol Ther, 2018, 19(9):786-796

PubMed: 30024813 ( click the link to review the publication )

Cancer Lett, 2018, 432:84-92

PubMed: 29859298 ( click the link to review the publication )

Cell Death Dis, 2017, 8(10):e3070

PubMed: 28981112 ( click the link to review the publication )

Theranostics, 2017, 7(17):4340-4349

PubMed: 29158830 ( click the link to review the publication )

Acta Pharmacol Sin, 2017, 38(7):1038-1047

PubMed: 28414200 ( click the link to review the publication )

Oncogene, 2013, 32(47):5377-87

PubMed: 23934192 ( click the link to review the publication )

4 Customer Reviews

PARP1 silencing rescues PARP1/2 inhibitor sensitivity in the ERCC1-deficient population. Effect of PARP1 knockdown by siRNA on sensitivity of ERCC1-isogenic cell lines to niraparib. Cells were reverse-transfected with PARP1 siRNA and drug was added 48 h after transfection. Cells were exposed to the drug for 5 days. Error bars represent the s.d. from the mean of three independent experiments.

Oncogene 2013 32(47):5377-87. Niraparib (MK-4827) purchased from Selleck.
Western Blot data testing protein expression after treatment with Olaparib, Niraparib, and Talazoparib on Brca1-deficient cell line in W780 cells.

Theranostics, 2017, 7(17):4340-4349. Niraparib (MK-4827) purchased from Selleck.
Co-treatment of miR-489-3p with olaparib or niraparib followed by SDS-PAGE analysis to detect MEK1 expression shows that MEK1 and pMEK1 are reduced with 25 μM olaparib or niraparib treatment alone. Since miR-489-3p targets MEK1, this phenomenon is amplified in co-treatment conditions for both PARP inhibitors in OVCAR-3 and MDA-MB-231.

Cancer Lett, 2018, 432:84-92. Niraparib (MK-4827) purchased from Selleck.
PAR synthesis is detected by immunofluorescence staining in A2780 and HO8910 treated with different concentration of berberine alone or in combination with niraparib (10 μM) for 48 h. Representative examples of immunofluorescence staining of PAR. Scale bar, 20 μm.

Cell Death Dis, 2017, 8(10):e3070. Niraparib (MK-4827) purchased from Selleck.

Purity & Quality Control

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Biological Activity

Description

Targets

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

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 Data

Cell Lines	Assay Type	Incubation Time	Activity Description	PMID
HeLa cells	NVS0Z2oxTnWwY4Tpc44h[XO\|YYm=		M1j0R2lvcGmkaYTpc44hd2ZiUFHSVEBqdiCqeXTyc4dmdiCyZYLvfIll\S2rbnT1Z4VlKGi3bXHuJGhmVGFiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDEUmEu\GGvYXflMYlv\HWlZXSgVGFTgWyjdHnvckwhTUN3ME2wMlAxPCEQvF2=	NEX3VFIyQTh5M{m4NS=>
A549 cells	MX\DfZRwfG:6aXPpeJkh[XO\|YYm=	MVy1MVch\GG7cx?=	NH\wS5ZEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBCPTR7IHPlcIx{KHS{YX7z[oVkfGWmIIfpeIghSlKFQUKgd4hTVkFiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iClZXzsJJBzd2yrZnXyZZRqd25iYX\0[ZIhPSC2bzC3JIRigXNiYomgR4VtdFSrdHXyMWJtfWViYYPzZZktKEOFNUC9NE4xOTFizszN	M33kO\|I2PzZzMEm2
MDA-MB-436 cells	MWHQdo9tcW[ncnH0bY9vKGG\|c3H5	NHroZ2M3KGSjeYO=	M1yzfGFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTVTBMW1DNTR\|NjDj[YxteyCneIDy[ZN{cW6pIFLSR2EyKDV\|OU[gL{AyTz6DIH31eIFvfCCjZoTldkA3KGSjeYOgZpkh[2WubDD0bZRmei2kbIXlJIF{e2G7LDDDR\|UxRTF6IH7N	Mn:zNVk5PzN7OEG=
SUM1315MO2 cells	MV;DfZRwfG:6aXPpeJkh[XO\|YYm=	NWH0eZBSOTJiZHH5dy=>	NYjPS\|ZGS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hW1WPMUOxOW1QOiClZXzsd{Bk[XK{eXnu[{BDWkODMTDteZRidnRiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iClZXzsJJBzd2yrZnXyZZRqd25iYX\0[ZIhOTJiZHH5d{BjgSCFZXzsWIl1\XJvQnz1[UBie3OjeTygR2M2OD1yLkCyJO69VQ>?	MnXaNlU4PjFyOU[=
DoTc2-4510 cells	NF;te4REgXSxdH;4bYNqfHliYYPzZZk>	MYC1MVch\GG7cx?=	M2nsNGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGRwXGN{LUS1NVAh[2WubIOgZ4FzenmrbnegRnJESTJibYX0ZY51KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4Yh[2WubDDwdo9tcW[ncnH0bY9vKGGodHXyJFUhfG9iNzDkZZl{KGK7IFPlcIxVcXSncj3CcJVmKGG\|c3H5MEBESzVyPUCuNFI{KM7:TR?=	NXzOXoFPOjV5NkGwPVY>
SUM149PT cells	MnWxR5l1d3SxeHnjbZR6KGG\|c3H5	M4ThTlUuPyCmYYnz	NUDLOZhjS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hW1WPMUS5VHQh[2WubIOgZ4FzenmrbnegRnJESTFibYX0ZY51KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4Yh[2WubDDwdo9tcW[ncnH0bY9vKGGodHXyJFUhfG9iNzDkZZl{KGK7IFPlcIxVcXSncj3CcJVmKGG\|c3H5MEBESzVyPUCuNFI1KM7:TR?=	M3vpb\|I2PzZzMEm2
UWB1.289 cells	MoTtR5l1d3SxeHnjbZR6KGG\|c3H5	NIHqWmk2NTdiZHH5dy=>	MXHDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDVW2IyNjJ6OTDj[YxteyClYYLyfYlv\yCEUlPBNUBufXSjboSgZZN{\XO\|ZXSgZZMhcW6qaXLpeIlwdiCxZjDj[YxtKHC{b3zp[oVz[XSrb36gZYZ1\XJiNTD0c{A4KGSjeYOgZpkhS2WubGTpeIVzNUKudXWgZZN{[XluIFPDOVA:OC5yNU[g{txO	MUGyOVc3OTB7Nh?=
Capan1 cells	MofRR5l1d3SxeHnjbZR6KGG\|c3H5		NEC0bGNEgXSxdH;4bYNqfHliYXfhbY5{fCCEUlPBNk1l\W[rY3nlcpQhcHWvYX6gR4Fx[W5zIHPlcIx{NCCFQ{WwQVAvODlizszN	NIfEdG4zPTd4MUC5Oi=>
Jurkat cells	MXHGeY5kfGmxbjDhd5NigQ>?		Ml;sTY5pcWKrdHnvckBw\iCSQWLQNUBqdiCqdX3hckBLfXKtYYSgZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJI9nKGOnbHygeoli[mmuaYT5JIFnfGW{IEm2JIhzeyCkeTDNWHMh[XO\|YYmgbY4heHKnc3XuZ4Uhd2ZiMUCwJJVOKG:oIITlcY97d2yxbXnk[UwhTUN3ME2wMlIh\|ryP	M3\qV\|I{QDVyMUm5
BT20 cells	M2XtSGN6fG:2b4jpZ4l1gSCjc4PhfS=>	NUDLe292PS15IHThfZM>	NGLmeZdEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBDXDJyIHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4Yh[2WubDDwdo9tcW[ncnH0bY9vKGGodHXyJFUhfG9iNzDkZZl{KGK7IFPlcIxVcXSncj3CcJVmKGG\|c3H5MEBESzVyPUKuNkDPxE1?	M1K2TlI2PzZzMEm2
A2780 cells	NE\zXlNHfW6ldHnvckBie3OjeR?=		MmrYTY5pcWKrdHnvckBw\iCSQWLQJIlvKGi3bXHuJGEzPzhyIHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4YhcHmmcn;n[Y4heGW{b4jp[IUucW6mdXPl[EBRSVK7bHH0bY9vKGK7IHPlcIwu[mG\|ZXSgZZN{[Xl?	MnHkNlU4PjFyOU[=

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	c-PARP /c-caspase 3 / γ-H2AX; PubMed: 29158830 Theranostics Western Blot data testing protein expression after treatment with Olaparib, Niraparib, and Talazoparib on Brca1-deficient cell line in W0069 cells.	29158830
Immunofluorescence	Rad51 / Geminin; PubMed: 27614696 Gynecol Oncol Immunofluorescence microscopy of niraparib-treated PDX cells (PH039) and irradiated cells showing RAD51 foci (arrow) within geminin positive cells and lack of RAD51 foci formation in control cells.	27614696

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].

Protocol

Cell Research:^[2]	+ Expand 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. (Only for Reference)
Animal Research:^[1]	+ Expand Animal Models: Female nude mice Formulation: 0.5% Methocel in deionized water Dosages: 25 mg/kg twice daily or 50 mg/kg once daily Administration: oral administration (Only for Reference)

Cell Research:^[2]

+ Expand

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.
(Only for Reference)

Animal Research:^[1]

+ Expand

Animal Models: Female nude mice
Formulation: 0.5% Methocel in deionized water
Dosages: 25 mg/kg twice daily or 50 mg/kg once daily
Administration: oral administration
(Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	64 mg/mL (199.75 mM)
	Ethanol	64 mg/mL (199.75 mM)
	Water	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 10% DMSO+40% PEG 300+5% Tween 80+ddH2O For best results, use promptly after mixing.	10mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download Niraparib (MK-4827) SDF

Molecular Weight	320.39
Formula	C₁₉H₂₀N₄O
CAS No.	1038915-60-4
Storage	3 years -20°C powder
Storage	2 years -80°C in solvent
Synonyms

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Clinical Trial Information (data from https://clinicaltrials.gov, updated on )

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03368729	Not yet recruiting	Drug: Niraparib\|Drug: Trastuzumab	Metastatic Breast Cancer\|HER2 Positive Breast Carcinoma	University of Alabama at Birmingham\|Translational Breast Cancer Research Consortium\|Tesaro Inc.\|Susan G. Komen Breast Cancer Foundation\|Breast Cancer Research Foundation of Alabama\|VFoundation	November 2019	Phase 1\|Phase 2
NCT03644342	Recruiting	Drug: Nirapaib	Metastatic Carcinoma of the Cervix	Michelle S Ludwig\|Tesaro Inc.\|Baylor College of Medicine	July 15 2019	Phase 1\|Phase 2
NCT03891615	Not yet recruiting	Drug: Niraparib\|Drug: Osimertinib	Lung Cancer	Massachusetts General Hospital\|Tesaro Inc.	April 30 2019	Phase 1
NCT03752216	Recruiting	Drug: Niraparib	Ovarian Cancer	ARCAGY/ GINECO GROUP\|Tesaro Inc.	April 3 2019	Phase 4
NCT03895788	Recruiting	Drug: niraparib\|Drug: Brivanib	Ovarian Cancer	Hunan Cancer Hospital	January 14 2019	Phase 1
NCT03695380	Recruiting	Drug: Cobimetinib\|Drug: Niraparib\|Drug: Atezolizumab	OVARIAN CANCER	Hoffmann-La Roche	January 9 2019	Phase 1

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.

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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.

PARP Signaling Pathway Map

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Niraparib (MK-4827)

Cited by 13 Publications

4 Customer Reviews

Purity & Quality Control

Choose Selective PARP Inhibitors

Biological Activity

Protocol

References

Solubility (25°C)

Chemical Information Download Niraparib (MK-4827) SDF

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Molecular Weight Calculator

Total Molecular Weight: g/mol

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Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on )

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Frequently Asked Questions

PARP Signaling Pathway Map

Related PARP Products

Choose Your Country or Region

By Signaling Pathways

By product type

Niraparib (MK-4827)

Cited by 13 Publications

4 Customer Reviews

Purity & Quality Control

Choose Selective PARP Inhibitors

Biological Activity

Protocol

References

Solubility (25°C)

Chemical Information Download Niraparib (MK-4827) SDF

Bio Calculators

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Dilution Calculator

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

The Serial Dilution Calculator Equation

Serial Dilutions

Computed Result

Molecular Weight Calculator

Total Molecular Weight: g/mol

Instructions to calculate molar mass (molecular weight) of a chemical compound:

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on )

Tech Support

Frequently Asked Questions

PARP Signaling Pathway Map

Related PARP Products

Concentration _(start) x Volume _(start) = Concentration _(final) x Volume _(final)