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 1 Publication

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

PubMed: 23934192

1 Customer Review

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.

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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	NInaUmVHfW6ldHnvckBie3OjeR?=		NHHWcJJKdmirYnn0bY9vKG:oIGDBVnAhcW5iaInkdo9o\W5icHXyc5hq\GVvaX7keYNm\CCqdX3hckBJ\UyjIHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gSG5CNWSjbXHn[U1qdmS3Y3XkJHBCWnmuYYTpc44tKEWFNUC9NE4xODRizszN	NIXuSHkyQTh5M{m4NS=>
A549 cells	NU[z[oZDS3m2b4TvfIlkcXS7IHHzd4F6	NFrjclc2NTdiZHH5dy=>	NXvwS\|RuS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hSTV2OTDj[YxteyC2cnHud4Zm[3SnZDD3bZRpKEKUQ1GyJJNpWk6DIHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiY3XscEBxem:uaX\ldoF1cW:wIHHmeIVzKDVidH:gO{Bl[Xm\|IHL5JGNmdGyWaYTldk1DdHWnIHHzd4F6NCCFQ{WwQVAvODFzIN88US=>	NY[xVIJPOjV5NkGwPVY>
MDA-MB-436 cells	Mk\WVJJwdGmoZYLheIlwdiCjc4PhfS=>	M4jiR\|Yh\GG7cx?=	M3S5[mFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTVTBMW1DNTR\|NjDj[YxteyCneIDy[ZN{cW6pIFLSR2EyKDV\|OU[gL{AyTz6DIH31eIFvfCCjZoTldkA3KGSjeYOgZpkh[2WubDD0bZRmei2kbIXlJIF{e2G7LDDDR\|UxRTF6IH7N	Mn3INVk5PzN7OEG=
SUM1315MO2 cells	NELxcY9EgXSxdH;4bYNqfHliYYPzZZk>	Mn;6NVIh\GG7cx?=	Mn;OR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV3VOOTNzNV3PNkBk\WyuczDjZZJzgWmwZzDCVmNCOSCvdYThcpQh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBk\WyuIIDyc4xq\mW{YYTpc44h[W[2ZYKgNVIh\GG7czDifUBE\WyuVHn0[ZIuSmy3ZTDhd5NigSxiQ1O1NF0xNjB{IN88US=>	M1Ty[lI2PzZzMEm2
DoTc2-4510 cells	MlzpR5l1d3SxeHnjbZR6KGG\|c3H5	NX\HToZKPS15IHThfZM>	MnTnR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gSI9V[zJvNEWxNEBk\WyuczDjZZJzgWmwZzDCVmNCOiCvdYThcpQh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBk\WyuIIDyc4xq\mW{YYTpc44h[W[2ZYKgOUB1dyB5IHThfZMh[nliQ3XscHRqfGW{LVLseYUh[XO\|YYmsJGNEPTB;MD6wNlMh\|ryP	NWfPbVBOOjV5NkGwPVY>
SUM149PT cells	NHr0dlZEgXSxdH;4bYNqfHliYYPzZZk>	NFKxVXM2NTdiZHH5dy=>	M1nZeWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJHNWVTF2OWDUJINmdGy\|IHPhdpJ6cW6pIFLSR2EyKG23dHHueEBie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJINmdGxicILvcIln\XKjdHnvckBi\nSncjC1JJRwKDdiZHH5d{BjgSCFZXzsWIl1\XJvQnz1[UBie3OjeTygR2M2OD1yLkCyOEDPxE1?	MUmyOVc3OTB7Nh?=
UWB1.289 cells	MVnDfZRwfG:6aXPpeJkh[XO\|YYm=	NVS5XYFyPS15IHThfZM>	M2OwfmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJHVYSjFwMki5JINmdGy\|IHPhdpJ6cW6pIFLSR2EyKG23dHHueEBie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJINmdGxicILvcIln\XKjdHnvckBi\nSncjC1JJRwKDdiZHH5d{BjgSCFZXzsWIl1\XJvQnz1[UBie3OjeTygR2M2OD1yLkC1OkDPxE1?	M2TZVFI2PzZzMEm2
Capan1 cells	MX7DfZRwfG:6aXPpeJkh[XO\|YYm=		NFOwcm5EgXSxdH;4bYNqfHliYXfhbY5{fCCEUlPBNk1l\W[rY3nlcpQhcHWvYX6gR4Fx[W5zIHPlcIx{NCCFQ{WwQVAvODlizszN	MXWyOVc3OTB7Nh?=
Jurkat cells	NHHJXXFHfW6ldHnvckBie3OjeR?=		MYHJcohq[mm2aX;uJI9nKFCDUmCxJIlvKGi3bXHuJGp2emujdDDj[YxteyCjc4Pld5Nm\CCjczDy[YR2[3Srb36gc4Yh[2WubDD2bYFjcWyrdImgZYZ1\XJiOU[gbJJ{KGK7IF3UV{Bie3OjeTDpckBxemW\|ZX7j[UBw\iBzMECgeW0hd2ZidHXtc5pwdG:vaXTlMEBGSzVyPUCuNkDPxE1?	NYfkW4o2OjN6NUCxPVk>
BT20 cells	NH;CVXhEgXSxdH;4bYNqfHliYYPzZZk>	NHfCb282NTdiZHH5dy=>	M{fKSmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGJVOjBiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBk\WyuIIDyc4xq\mW{YYTpc44h[W[2ZYKgOUB1dyB5IHThfZMh[nliQ3XscHRqfGW{LVLseYUh[XO\|YYmsJGNEPTB;Mj6yJO69VQ>?	MlXiNlU4PjFyOU[=
A2780 cells	M1rw[mZ2dmO2aX;uJIF{e2G7		MknGTY5pcWKrdHnvckBw\iCSQWLQJIlvKGi3bXHuJGEzPzhyIHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4YhcHmmcn;n[Y4heGW{b4jp[IUucW6mdXPl[EBRSVK7bHH0bY9vKGK7IHPlcIwu[mG\|ZXSgZZN{[Xl?	NYrn[ph3OjV5NkGwPVY>

... Click to View More Cell Line Experimental Data

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 2018-10-19)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03326193	Recruiting	Ovarian Cancer\|Fallopian Tube Cancer\|Primary Peritoneal Carcinoma	Tesaro Inc.	January 9 2018	Phase 2
NCT03705156	Recruiting	Platinum-sensitive Relapsed Ovarian Cancer	Zai Lab (Shanghai) Co. Ltd.	June 8 2017	Phase 3
NCT03016338	Recruiting	Endometrial Cancer	University Health Network Toronto\|Tesaro Inc.	November 6 2017	Phase 2
NCT03497429	Active not recruiting	Advanced Solid Tumors	Takeda	April 5 2018	Phase 1
NCT03695380	Not yet recruiting	OVARIAN CANCER	Hoffmann-La Roche	December 31 2018	Phase 1
NCT03586661	Not yet recruiting	Deleterious BRCA1 Gene Mutation\|Deleterious BRCA2 Gene Mutation\|Endometrial Adenocarcinoma\|High Grade Ovarian Serous Adenocarcinoma\|Primary Peritoneal High Grade Serous Adenocarcinoma\|Recurrent Endometrial Carcinoma\|Recurrent Fallopian Tube Carcinoma\|Recurrent Ovarian Carcinoma\|Recurrent Primary Peritoneal Carcinoma	M.D. Anderson Cancer Center\|National Cancer Institute (NCI)	October 31 2018	Phase 1

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How to reconstitute the compound for in vivo studies?
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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 1 Publication

1 Customer Review

Purity & Quality Control

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References

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Chemical Information Download Niraparib (MK-4827) SDF

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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2018-10-19)

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Niraparib (MK-4827)

Cited by 1 Publication

1 Customer Review

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 2018-10-19)

Tech Support

Frequently Asked Questions

PARP Signaling Pathway Map

Related PARP Products

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