Niraparib (MK-4827)

製品コードS2741 バッチS274106

印刷

化学情報

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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	2.500mg/ml (7.80mM)	Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <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, 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, this compound 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^[2].
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^[1]. It was well tolerated in vivo and demonstrated efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer^[2].

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：

HR eye & MMR eye: one-day assessment of DNA repair-defective tumors eligible for targeted therapy [ Nat Commun, 2025, 16(1):4239]	PubMed: 40355434
Germline analysis of an international cohort of pediatric diffuse midline glioma patients [ Neuro Oncol, 2025, noaf061]	PubMed: 40072012
XRCC1 mediates PARP1- and PAR-dependent recruitment of PARP2 to DNA damage sites [ Nucleic Acids Res, 2025, 53(4)gkaf086]	PubMed: 39970298
Niraparib restricts intraperitoneal metastases of ovarian cancer by eliciting CD36-dependent ferroptosis [ Redox Biol, 2025, 80:103528]	PubMed: 39922130
Combining Multiplexed CRISPR/Cas9-Nickase and PARP Inhibitors Efficiently and Precisely Targets Cancer Cells [ Cancer Res, 2025, 10.1158/0008-5472.CAN-24-2938]	PubMed: 40327605
ZNF251 haploinsufficiency confers PARP inhibitors resistance in BRCA1-mutated cancer cells through activation of homologous recombination [ Cancer Lett, 2025, 613:217505]	PubMed: 39892701
PARP inhibitor-induced anti-tumour chemokine response is suppressed by dipeptidyl peptidase 4 (DPP4) in ovarian cancer [ Br J Cancer, 2025, 10.1038/s41416-025-03076-4]	PubMed: 40579444
LEF1 confers resistance to DNA-damaging chemotherapies through upregulation of PARP1 and NUMA1 in ovarian cancer [ Oncogene, 2025, 10.1038/s41388-025-03561-3]	PubMed: 40931049
PARP inhibitors elicit distinct transcriptional programs in homologous recombination competent castration-resistant prostate cancer [ Mol Oncol, 2025, 10.1002/1878-0261.70098]	PubMed: 40915979
Homologous Repair-Deficient Pancreatic Cancer: Refined Targeting of DNA Damage Response is an Effective Therapeutic Strategy [ United Eur Gastroent, 2025, 13(7):1328-1342]	PubMed: 40823818

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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