Niraparib (MK-4827)

製品コードS2741 バッチS274103

印刷

化学情報

Chemical Structure Synonyms Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C19H20N4O
分子量 320.39 CAS No. 1038915-60-4
Solubility (25°C)* 体外 DMSO (warmed with 50ºC water bath) 64 mg/mL (199.75 mM)
Ethanol 64 mg/mL (199.75 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 ニラパリブ (Niraparib (MK-4827)) は PARP1/2 の選択的阻害剤 (IC50 = 3.8 nM/2.1 nM) であり、変異型 BRCA-1 および BRCA-2 を持つ癌細胞で高い活性を示します。PARP3, V-PARP, Tank1 に比べて 330 倍以上の選択性があります。 ニラパリブは PARP-DNA 複合体を形成し、DNA損傷、アポトーシス (apoptossis)、および細胞死を引き起こします。臨床フェーズ 3。
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.

プロトコル(参考用のみ)

細胞アッセイ 細胞株 HeLa BRCA1-silenced cells
濃度 serial dilutions
反応時間 7 days
実験の流れ 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.
動物実験 動物モデル Female nude mice
投薬量 25 mg/kg twice daily or 50 mg/kg once daily
投与方法 oral administration

参考

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

カスタマーフィードバック

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

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

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

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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