Niraparib (MK-4827)

Catalog No.S2741 Batch:S274104

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Technical Data

Formula

C19H20N4O
Molecular Weight 320.39 CAS No. 1038915-60-4
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)
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.
* <1 mg/ml means slightly soluble or insoluble.
* 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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. This compound can form PARP–DNA complexes resulting in DNA damage, apoptosis, and cell death. Phase 3.
Targets
PARP2 [1]
(Cell-free assay)		 PARP1 [1]
(Cell-free assay)
2.1 nM 3.8 nM
In vitro In a whole cell assay, Niraparib (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, this compound 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, it 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, it displayed CC50 = 18 nM, while in CAPAN-1 human pancreatic adenocarcinoma cells, which are BRCA-2 mutant, it 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.
In vivo Niraparib (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. It was well tolerated in vivo and demonstrated efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer.

Protocol (from reference)

Cell Assay:[2]
  • 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. Niraparib (MK-4827) was 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.
Animal Study:[1]
  • Animal Models

    Female nude mice

  • Dosages

    25 mg/kg twice daily or 50 mg/kg once daily

  • Administration

    oral administration

References

  • https://pubmed.ncbi.nlm.nih.gov/22127459/
  • https://pubmed.ncbi.nlm.nih.gov/19873981/

Customer Product Validation

<div>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.</div><div> </div>

Data from [ Oncogene , 2013 , 32(47):5377-87 ]

Western Blot data testing protein expression after treatment with Olaparib, Niraparib, and Talazoparib on Brca1-deficient cell line in W780 cells.

Data from [ , , Theranostics, 2017, 7(17):4340-4349 ]

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.

Data from [ , , Cancer Lett, 2018, 432:84-92 ]

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.

Data from [ , , Cell Death Dis, 2017, 8(10):e3070 ]

Selleck's Niraparib (MK-4827) Has Been Cited by 123 Publications

Pharmacological effects of Niraparib and its combination with angiogenic inhibitor in ovarian cancer [ Journal of Cancer, October 16, 2023, 3397-3403] PubMed: 37268756
PCBP2 Mediates Olaparib Resistance in Breast Cancer by Inhibiting m6A Methylation to Stabilize PARP1 mRNA [ Cancer Research, October 15, 2025, 3949-3965] PubMed: 40773674
GX15-070 enhances niraparib efficacy in ovarian cancer by promoting a shift in Mcl1-mediated DNA repair pathway from HR to NHEJ [ Journal of Translational Medicine, November 11, 2025, 1262] PubMed: 41220001
The irreversible ERBB1/2/4 inhibitor neratinib interacts with the PARP1 inhibitor niraparib to kill ovarian cancer cells [ Cancer Biology & Therapy, March 6, 2018, 525-533] PubMed: 29405820
PARP inhibitor shuts down the global translation of thyroid cancer through promoting Pol II binding to DIMT1 pause [ International Journal of Biological Sciences, July 31, 2023, 3970-3986] PubMed: 37564214
Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy [ Cancer Discovery, July 1, 2019, 852-871] PubMed: 31053628
Induction of apoptosis in MDA-MB-231 breast cancer cells by a PARP1-targeting PROTAC small molecule [ Chemical Communications, December 5, 2018, 369-372] PubMed: 30540295
Proteomic Analysis Reveals Low-Dose PARP Inhibitor-Induced Differential Protein Expression in BRCA1-Mutated High-Grade Serous Ovarian Cancer Cells [ Journal of the American Society for Mass Spectrometry, December 27, 2021, 242-250] PubMed: 34958553
Niraparib Suppresses Cholangiocarcinoma Tumor Growth by Inducing Oxidative and Replication Stress [ Cancers, August 31, 2021, 4405] PubMed: 34503215
Exosomal miR-664a-5p as a therapeutic target biomarker for PARP inhibitor response in prostate cancer [ American Journal of Cancer Research, August 25, 2024, 3789-3799] PubMed: 39267686

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SHIPPING AND STORAGE
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