ホームページ DNA Damage/DNA Repair PARP inhibitor - Apoptosis related activator Niraparib (MK-4827) For research use only.

Niraparib (MK-4827)

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。

Niraparib (MK-4827)化学構造

CAS No. 1038915-60-4

サイズ 価格(税別) 在庫状況
10mM (1mL in DMSO) JPY 41500 国内在庫あり
JPY 25500 国内在庫あり
JPY 86500 国内在庫あり
JPY 145500 国内在庫あり
JPY 295500 国内在庫なし(納期7~10日)

代表番号: 045-509-1970|電子メール：[email protected]
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Niraparib (MK-4827)関連製品

シグナル伝達経路

PARP Signaling Pathways

PARPシグナル伝達経路

PARP阻害剤の選択性比較

Cell Data

Cell Lines Assay Type Concentration Incubation Time 活性情報 PMID
Antitumor assay MDA-MB-436 50 mg/kg 33 days Antitumor activity against human MDA-MB-436 cells expressing BRCA1 5396 + 1G>A mutant xenografted in CD1 mouse assessed as tumor regression at 50 mg/kg, po bid for 33 days 19873981
Antitumor assay MDA-MB-436 100 mg/kg 33 days Antitumor activity against human MDA-MB-436 cells expressing BRCA1 5396 + 1G>A mutant xenografted in CD1 mouse assessed as tumor regression at 100 mg/kg, po qd for 33 days 19873981
Antitumor assay MDA-MB-436 80 mg/kg 1 to 2 weeks Antitumor activity against human MDA-MB-436 cells harboring BRCA1 mutant xenografted in immunocompromised mouse assessed as tumor growth inhibition at 80 mg/kg, po qd for 1 to 2 weeks 25761096
Antitumor assay MDA-MB-436 80 mg/kg 4 weeks Antitumor activity against human MDA-MB-436 cells harboring BRCA1 mutant xenografted in immunocompromised mouse assessed as complete and sustained tumor regression at 80 mg/kg, po qd for 4 weeks 25761096
Antitumor assay MDA-MB-436 80 mg/kg 3 weeks Antitumor activity against human MDA-MB-436 cells harboring BRCA1 mutant xenografted in immunocompromised mouse assessed as tumor shrinkage at 80 mg/kg, po qd for 3 weeks 25761096
Antitumor assay MDA-MB-436 50 mg/kg Antitumor activity against human MDA-MB-436 cells harboring BRCA1 mutant xenografted in immunocompromised mouse assessed as tumor growth inhibition at 50 mg/kg, po administered daily 25761096
UWB1.289 cells Cytotoxicity assay 5-7 days Cytotoxicity against human UWB1.289 cells carrying BRCA1 mutant assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50=0.056 μM 25761096
SUM149PT cells Cytotoxicity assay 5-7 days Cytotoxicity against human SUM149PT cells carrying BRCA1 mutant assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50=0.024 μM 25761096
DoTc2-4510 cells Cytotoxicity assay 5-7 days Cytotoxicity against human DoTc2-4510 cells carrying BRCA2 mutant assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50=0.023 μM 25761096
SUM1315MO2 cells Cytotoxicity assay 12 days Cytotoxicity against human SUM1315MO2 cells carrying BRCA1 mutant assessed as inhibition of cell proliferation after 12 days by CellTiter-Blue assay, CC50=0.02 μM 25761096
MDA-MB-436 cells Proliferation assay 6 days Antiproliferative activity against human MDA-MB-436 cells expressing BRCA1 5396 + 1G>A mutant after 6 days by cell titer-blue assay, CC50=18 nM 19873981
A549 cells Cytotoxicity assay 5-7 days Cytotoxicity against human A549 cells transfected with BRCA2 shRNA assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50=0.011 μM 25761096
BT20 cells Cytotoxicity assay 5-7 days Cytotoxicity against human BT20 cells assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50=2.2 μM 25761096
Antiproliferative assay HeLa 7 days Antiproliferative activity against BRCA1 deficient human HeLa cells after 7 days by cell titer-blue assay, CC50 = 0.033 μM. 19873981
Antiproliferative assay Capan1 13 days Antiproliferative activity against human Capan1 cells expressing BRCA2 6174delT mutation and loss of wild-type allele after 13 days by cell titer-blue assay, CC50 = 0.09 μM. 19873981
Antiproliferative assay HeLa 7 days Antiproliferative activity against human HeLa cells expressing wild type BRCA1 after 7 days by cell titer-blue assay, CC50 = 0.86 μM. 19873981
Function assay Jurkat 96 hrs Inhibition of PARP1 in human Jurkat cells assessed as reduction of cell viability after 96 hrs by MTS assay, EC50 = 31 μM. 23850199
Cytotoxicity assay HeLa 5 to 7 days Cytotoxicity against human HeLa cells transfected with BRCA1 shRNA assessed as reduction of cell viability after 5 to 7 days by CellTiter-Blue assay, CC50 = 0.034 μM. 25761096
Cytotoxicity assay HeLa 5 to 7 days Cytotoxicity against wild type human HeLa cells assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50 = 0.852 μM. 25761096
Cytotoxicity assay UWB1.289 5 to 7 days Cytotoxicity against human UWB1.289 cells expressing BRCA1 assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50 = 0.975 μM. 25761096
Cytotoxicity assay A549 5 to 7 days Cytotoxicity against wild type human A549 cells assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50 = 1.76 μM. 25761096
Capan1 cells Cytotoxicity assay Cytotoxicity against BRCA2-deficient human Capan1 cells, CC50=0.09 μM 25761096
HeLa cells Function assay Inhibition of PARP in hydrogen peroxide-induced human HeLa cells assessed as inhibition DNA-damage-induced PARylation, EC50=0.004 μM 19873981
Jurkat cells Function assay Inhibition of PARP1 in human Jurkat cells assessed as reduction of cell viability after 96 hrs by MTS assay in presence of 100 uM of temozolomide, EC50=0.2 μM 23850199
Function assay HeLa Inhibition of PARP in hydrogen peroxide-induced human HeLa cells assessed as inhibition DNA-damage-induced PARylation, EC90 = 0.045 μM. 19873981
Function assay CAPAN-1 Inhibition of PARP in BRCA2-deficient human CAPAN-1 cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, IC50 = 0.0035 μM. 25761096
Function assay HeLa Inhibition of PARP in human HeLa cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, EC50 = 0.004 μM. 25761096
Function assay A2780 Inhibition of PARP in human A2780 cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, IC50 = 0.004 μM. 25761096
Cytotoxicity assay MDA-MB-436 Cytotoxicity against human MDA-MB-436 cells carrying BRCA1 mutant assessed as inhibition of cell proliferation, CC50 = 0.018 μM. 25761096
Function assay HeLa Inhibition of PARP in human HeLa cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, IC90 = 0.046 μM. 25761096
Function assay CAPAN-1 Inhibition of PARP in BRCA2-deficient human CAPAN-1 cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, IC90 = 0.05 μM. 25761096
Function assay A2780 Inhibition of PARP in human A2780 cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, IC90 = 0.052 μM. 25761096
Cytotoxicity assay Capan1 Cytotoxicity against BRCA2-deficient human Capan1 cells, EC50 = 0.65 μM. 26652717
qHTS assay TC32 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
qHTS assay A673 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
qHTS assay NB1643 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
qHTS assay A673 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
qHTS assay BT-37 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells 29435139
qHTS assay SK-N-MC qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
qHTS assay NB-EBc1 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
qHTS assay LAN-5 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
qHTS assay SK-N-MC qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells 29435139
qHTS assay TC32 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells 29435139
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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。
Targets
PARP2 [1]
(Cell-free assay)		 PARP1 [1]
(Cell-free assay)
2.1 nM 3.8 nM
In Vitro
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].
細胞実験 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. 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.
実験結果図 Methods Biomarkers 結果図 PMID
Western blot c-PARP /c-caspase 3 / γ-H2AX 29158830
Immunofluorescence Rad51 / Geminin 27614696
In Vivo
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].
動物実験 動物モデル Female nude mice
投与量 25 mg/kg twice daily or 50 mg/kg once daily
投与経路 oral administration
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05289648 Not yet recruiting
Endometrial Cancer|Serous Adenocarcinoma|Uterine Neoplasm
Sir Mortimer B. Davis - Jewish General Hospital
 May 1 2024 Early Phase 1
NCT06077877 Recruiting
Neoplasms
GlaxoSmithKline
 October 24 2023 Phase 1|Phase 2
NCT05666349 Withdrawn
Recurrent Glioblastoma
University College London|GlaxoSmithKline
 October 13 2023 Phase 1

化学情報

分子量 320.39 化学式

C19H20N4O
CAS No. 1038915-60-4 SDF Download Niraparib (MK-4827) SDFをダウンロードする
Smiles C1CC(CNC1)C2=CC=C(C=C2)N3C=C4C=CC=C(C4=N3)C(=O)N
保管

In vitro
Batch:

DMSO : 64 mg/mL ( (199.75 mM)； 吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 64 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量 濃度 体積 分子量

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

mg/kg g μL 匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH2O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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Handling Instructions

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よくある質問（FAQ）

質問1:
How to reconstitute the compound for in vivo studies?

回答
You can use the formulation 1% CMC-Na (suspension) for oral administration.

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