Niraparib (MK-4827)

Catalog No.S2741

Niraparib (MK-4827) Chemical Structure

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.

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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 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.
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 Concentration Incubation Time Formulation Activity Description PMID
HeLa cells MnHuSpVv[3Srb36gZZN{[Xl? Ml;lTY5pcWKrdHnvckBw\iCSQWLQJIlvKGi7ZILv[4VvKHCncn;4bYRmNWmwZIXj[YQhcHWvYX6gTIVN[SClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIFTORU1l[W2jZ3WtbY5lfWOnZDDQRXJ6dGG2aX;uMEBGSzVyPUCuNFA1KM7:TR?= NIfYPYIyQTh5M{m4NS=>
A549 cells MlTiR5l1d3SxeHnjbZR6KGG|c3H5 M1XB[lUuPyCmYYnz MoDQR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gRVU1QSClZXzsd{B1emGwc3\lZ5Rm\CC5aYToJGJTS0F{IIPoVm5CKGG|c3Xzd4VlKGG|IHnubIljcXSrb36gc4Yh[2WubDDwdo9tcW[ncnH0bY9vKGGodHXyJFUhfG9iNzDkZZl{KGK7IFPlcIxVcXSncj3CcJVmKGG|c3H5MEBESzVyPUCuNFEyKM7:TR?= MX6yOVc3OTB7Nh?=
MDA-MB-436 cells M4e0cHBzd2yrZnXyZZRqd25iYYPzZZk> NWL4O2pbPiCmYYnz MWrBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKE2GQT3NRk01OzZiY3XscJMh\XiycnXzd4lv\yCEUlPBNUA2Ozl4IDugNWc,SSCvdYThcpQh[W[2ZYKgOkBl[Xm|IHL5JINmdGxidHn0[ZIu[my3ZTDhd5NigSxiQ1O1NF0yQCCwTR?= M{Xrc|E6QDd|OUix
SUM1315MO2 cells MVfDfZRwfG:6aXPpeJkh[XO|YYm= M2TadFEzKGSjeYO= NF7YZ5JEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBUXU1zM{G1UW8zKGOnbHzzJINienK7aX7nJGJTS0FzIH31eIFvfCCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKGOnbHygdJJwdGmoZYLheIlwdiCjZoTldkAyOiCmYYnzJIJ6KEOnbHzUbZRmei2EbIXlJIF{e2G7LDDDR|UxRTBwMEKg{txO NHW5XogzPTd4MUC5Oi=>
DoTc2-4510 cells NILLUJhEgXSxdH;4bYNqfHliYYPzZZk> MnPTOU04KGSjeYO= NWfZe21IS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hTG:WY{KtOFUyOCClZXzsd{Bk[XK{eXnu[{BDWkODMjDteZRidnRiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iClZXzsJJBzd2yrZnXyZZRqd25iYX\0[ZIhPSC2bzC3JIRigXNiYomgR4VtdFSrdHXyMWJtfWViYYPzZZktKEOFNUC9NE4xOjNizszN MkS2NlU4PjFyOU[=
SUM149PT cells M{nMbGN6fG:2b4jpZ4l1gSCjc4PhfS=> NIXtOXU2NTdiZHH5dy=> MnjYR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV3VOOTR7UGSgZ4VtdHNiY3HydplqdmdiQmLDRVEhdXW2YX70JIF{e2W|c3XkJIF{KGmwaHnibZRqd25ib3[gZ4VtdCCycn;sbYZmemG2aX;uJIFnfGW{IEWgeI8hPyCmYYnzJIJ6KEOnbHzUbZRmei2EbIXlJIF{e2G7LDDDR|UxRTBwMEK0JO69VQ>? NH;FZpczPTd4MUC5Oi=>
UWB1.289 cells NXm2[JR1S3m2b4TvfIlkcXS7IHHzd4F6 M4PrclUuPyCmYYnz MWfDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDVW2IyNjJ6OTDj[YxteyClYYLyfYlv\yCEUlPBNUBufXSjboSgZZN{\XO|ZXSgZZMhcW6qaXLpeIlwdiCxZjDj[YxtKHC{b3zp[oVz[XSrb36gZYZ1\XJiNTD0c{A4KGSjeYOgZpkhS2WubGTpeIVzNUKudXWgZZN{[XluIFPDOVA:OC5yNU[g{txO M{nQflI2PzZzMEm2
Capan1 cells Ml3sR5l1d3SxeHnjbZR6KGG|c3H5 M1HuO2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KEKUQ1GyMYRm\mmlaXXueEBpfW2jbjDDZZBidjFiY3XscJMtKEOFNUC9NE4xQSEQvF2= NFPBW5QzPTd4MUC5Oi=>
Jurkat cells MWXGeY5kfGmxbjDhd5NigQ>? MYPJcohq[mm2aX;uJI9nKFCDUmCxJIlvKGi3bXHuJGp2emujdDDj[YxteyCjc4Pld5Nm\CCjczDy[YR2[3Srb36gc4Yh[2WubDD2bYFjcWyrdImgZYZ1\XJiOU[gbJJ{KGK7IF3UV{Bie3OjeTDpckBxemW|ZX7j[UBw\iBzMECgeW0hd2ZidHXtc5pwdG:vaXTlMEBGSzVyPUCuNkDPxE1? NUiwOpNUOjN6NUCxPVk>
BT20 cells NXvyOI4{S3m2b4TvfIlkcXS7IHHzd4F6 M33oSlUuPyCmYYnz MknkR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gRnQzOCClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJINmdGxicILvcIln\XKjdHnvckBi\nSncjC1JJRwKDdiZHH5d{BjgSCFZXzsWIl1\XJvQnz1[UBie3OjeTygR2M2OD1{LkKg{txO NH\sN2QzPTd4MUC5Oi=>
A2780 cells M4q4ZWZ2dmO2aX;uJIF{e2G7 M3\Xe2lvcGmkaYTpc44hd2ZiUFHSVEBqdiCqdX3hckBCOjd6MDDj[YxteyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKGi7ZILv[4VvKHCncn;4bYRmNWmwZIXj[YQhWEGUeXzheIlwdiCkeTDj[YxtNWKjc3XkJIF{e2G7 NYe0WVVrOjV5NkGwPVY>

... 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].


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)

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.

* 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

Molecular Weight 320.39


CAS No. 1038915-60-4
Storage powder
in solvent

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Clinical Trial Information

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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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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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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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID