Niraparib (MK-4827)

Name: Niraparib (MK-4827)
Brand: Selleck Chemicals
SKU: S2741
Rating: 5 (20 reviews)

For research use only. Not for use in humans.

Catalog No.S2741

20 publications

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.

Selleck's Niraparib (MK-4827) has been cited by 20 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 )

Nat Commun, 2019, 10(1):5661

PubMed: 31827092 ( click the link to review the publication )

Clin Cancer Res, 2019, 10.1158/1078-0432.CCR-19-2409

PubMed: 31831554 ( click the link to review the publication )

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

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

Mol Cancer Ther, 2019, 10.1158/1535-7163.MCT-19-0242

PubMed: 31534014 ( click the link to review the publication )

Endocrinology, 2019, 160(11):2600-2617

PubMed: 31322702 ( 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 )

Nat Commun, 2018, 9(1):176

PubMed: 29330466 ( click the link to review the publication )

Clin Cancer Res, 2018, 24(23):6066-6077

PubMed: 30061362 ( click the link to review the publication )

Elife, 2018, 7

PubMed: 30088474 ( 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 )

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	MXHGeY5kfGmxbjDhd5NigQ>?		NFvwbmhKdmirYnn0bY9vKG:oIGDBVnAhcW5iaInkdo9o\W5icHXyc5hq\GVvaX7keYNm\CCqdX3hckBJ\UyjIHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gSG5CNWSjbXHn[U1qdmS3Y3XkJHBCWnmuYYTpc44tKEWFNUC9NE4xODRizszN	NV7ubm5GOTl6N{O5PFE>
A549 cells	MWfDfZRwfG:6aXPpeJkh[XO\|YYm=	M4GzclUuPyCmYYnz	NICxepREgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBCPTR7IHPlcIx{KHS{YX7z[oVkfGWmIIfpeIghSlKFQUKgd4hTVkFiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iClZXzsJJBzd2yrZnXyZZRqd25iYX\0[ZIhPSC2bzC3JIRigXNiYomgR4VtdFSrdHXyMWJtfWViYYPzZZktKEOFNUC9NE4xOTFizszN	NVG0Zo97OjV5NkGwPVY>
MDA-MB-436 cells	M4f3ZnBzd2yrZnXyZZRqd25iYYPzZZk>	NIDHTpg3KGSjeYO=	M4XyW2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTVTBMW1DNTR\|NjDj[YxteyCneIDy[ZN{cW6pIFLSR2EyKDV\|OU[gL{AyTz6DIH31eIFvfCCjZoTldkA3KGSjeYOgZpkh[2WubDD0bZRmei2kbIXlJIF{e2G7LDDDR\|UxRTF6IH7N	MlfsNVk5PzN7OEG=
SUM1315MO2 cells	MlyxR5l1d3SxeHnjbZR6KGG\|c3H5	NHr1W5kyOiCmYYnz	MULDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDTWW0yOzF3TV:yJINmdGy\|IHPhdpJ6cW6pIFLSR2EyKG23dHHueEBie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJINmdGxicILvcIln\XKjdHnvckBi\nSncjCxNkBl[Xm\|IHL5JGNmdGyWaYTldk1DdHWnIHHzd4F6NCCFQ{WwQVAvODJizszN	NG\qT4wzPTd4MUC5Oi=>
DoTc2-4510 cells	MoHHR5l1d3SxeHnjbZR6KGG\|c3H5	MlzFOU04KGSjeYO=	MWnDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDEc3RkOi12NUGwJINmdGy\|IHPhdpJ6cW6pIFLSR2EzKG23dHHueEBie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJINmdGxicILvcIln\XKjdHnvckBi\nSncjC1JJRwKDdiZHH5d{BjgSCFZXzsWIl1\XJvQnz1[UBie3OjeTygR2M2OD1yLkCyN{DPxE1?	M1zn[FI2PzZzMEm2
SUM149PT cells	MULDfZRwfG:6aXPpeJkh[XO\|YYm=	MkC4OU04KGSjeYO=	MV\DfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDTWW0yPDmSVDDj[YxteyClYYLyfYlv\yCEUlPBNUBufXSjboSgZZN{\XO\|ZXSgZZMhcW6qaXLpeIlwdiCxZjDj[YxtKHC{b3zp[oVz[XSrb36gZYZ1\XJiNTD0c{A4KGSjeYOgZpkhS2WubGTpeIVzNUKudXWgZZN{[XluIFPDOVA:OC5yMkSg{txO	M{frO\|I2PzZzMEm2
UWB1.289 cells	MlHvR5l1d3SxeHnjbZR6KGG\|c3H5	NXvn[49nPS15IHThfZM>	MXLDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDVW2IyNjJ6OTDj[YxteyClYYLyfYlv\yCEUlPBNUBufXSjboSgZZN{\XO\|ZXSgZZMhcW6qaXLpeIlwdiCxZjDj[YxtKHC{b3zp[oVz[XSrb36gZYZ1\XJiNTD0c{A4KGSjeYOgZpkhS2WubGTpeIVzNUKudXWgZZN{[XluIFPDOVA:OC5yNU[g{txO	NYWxSVJSOjV5NkGwPVY>
Capan1 cells	Mnf6R5l1d3SxeHnjbZR6KGG\|c3H5		M1Hac2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KEKUQ1GyMYRm\mmlaXXueEBpfW2jbjDDZZBidjFiY3XscJMtKEOFNUC9NE4xQSEQvF2=	MonwNlU4PjFyOU[=
Jurkat cells	Ml73SpVv[3Srb36gZZN{[Xl?		MoPuTY5pcWKrdHnvckBw\iCSQWLQNUBqdiCqdX3hckBLfXKtYYSgZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJI9nKGOnbHygeoli[mmuaYT5JIFnfGW{IEm2JIhzeyCkeTDNWHMh[XO\|YYmgbY4heHKnc3XuZ4Uhd2ZiMUCwJJVOKG:oIITlcY97d2yxbXnk[UwhTUN3ME2wMlIh\|ryP	NVjxdlVuOjN6NUCxPVk>
BT20 cells	M4KyWWN6fG:2b4jpZ4l1gSCjc4PhfS=>	M{\hZ\|UuPyCmYYnz	MlH6R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gRnQzOCClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJINmdGxicILvcIln\XKjdHnvckBi\nSncjC1JJRwKDdiZHH5d{BjgSCFZXzsWIl1\XJvQnz1[UBie3OjeTygR2M2OD1{LkKg{txO	NYHyfGVkOjV5NkGwPVY>
A2780 cells	M4O4dGZ2dmO2aX;uJIF{e2G7		NXfRc\|RrUW6qaXLpeIlwdiCxZjDQRXJRKGmwIHj1cYFvKEF{N{iwJINmdGy\|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiaInkdo9o\W5icHXyc5hq\GVvaX7keYNm\CCSQWL5cIF1cW:wIHL5JINmdGxvYnHz[YQh[XO\|YYm=	MoTZNlU4PjFyOU[=

... 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]

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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]

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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
Smiles	NC(=O)C1=CC=CC2=C[N](N=C12)C3=CC=C(C=C3)C4CCCNC4

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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2019-10-14)

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

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)