Niraparib (MK-4827)
中文名称：尼拉帕尼
Niraparib (MK4827)是一种口服有效的选择性PARP-1和PARP-2抑制剂，可在有BRCA和PTEN功能缺陷的临床肿瘤模型中引起合成致死性。Niraparib 可形成PARP–DNA复合物并导致DNA损伤、凋亡和细胞死亡。Phase 3。
Niraparib (MK-4827) Chemical Structure
CAS: 1038915-60-4
产品质控
批次：
纯度：
99.97%
99.97
Niraparib (MK-4827)相关产品
相关信号通路图
细胞实验数据示例
| 细胞系 | 实验类型 | 给药浓度 | 孵育时间 | 活性描述 | 文献信息 |
|---|---|---|---|---|---|
| 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 | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | Niraparib (MK4827)是一种口服有效的选择性PARP-1和PARP-2抑制剂，可在有BRCA和PTEN功能缺陷的临床肿瘤模型中引起合成致死性。Niraparib 可形成PARP–DNA复合物并导致DNA损伤、凋亡和细胞死亡。Phase 3。 | ||||
|---|---|---|---|---|---|
| 靶点 |
|
| 体外研究(In Vitro) | ||||
| 体外研究活性 | 在完整细胞试验中，MK-4827抑制PARP的活性，EC50为4 nM，并抑制携带BRCA-1和BRCA-2突变的癌细胞的增殖，IC50为10-100 nM。它能有效地抑制PARP-1和PARP-2，IC分别为3.8 nM和2.1 nM。它对PARP-3, V-PARP和tankyrase-1的选择性低100倍以上，IC50分别为1300、330、570 nM。MK-4827能够抑制携带有天然BRCA-1和BRCA-2突变的癌细胞的增殖、通过RNA干扰抑制BRCA-1缺陷的Hela细胞的生长。在携带BRCA-1突变的MDA-MB-436人类乳腺腺癌的细胞中，MK-4827的CC50=18 nM；而在BRCA-2缺陷的CAPAN-1人胰腺癌细胞中，CC50=90 nM。而正常人类前列腺和乳腺上皮细胞对MK-4827具有耐药性，在微摩尔范围内具有抗凋亡作用，说明这些PARP抑制剂在具有BRCA-1和BRCA-2突变的癌细胞中具有选择性细胞毒性，对周围组织影响小[2]。 | |||
|---|---|---|---|---|
| 细胞实验 | 细胞系 | BRCA1基因沉默的Hela细胞 | ||
| 浓度 | 系列稀释浓度 | |||
| 孵育时间 | 7天 | |||
| 方法 | 将细胞置于96孔黑色viewplates中，细胞密度为300/孔，每孔含190 μLDMEM培养基(含10%胎牛血清，0.1 mg/mL青-链霉素双抗，2 mM L-谷氨酰胺)，在37℃、5% CO2的细胞培养箱中培养4小时。将系列稀释的抑制剂加入其中，每孔10 μL，使化合物浓度达到工作浓度、DMSO为0.5%。然后在细胞在细胞培养箱中培养7天。7天后，测定细胞活力。 | |||
| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | c-PARP /c-caspase 3 / γ-H2AX |
|
29158830 | |
| Immunofluorescence | Rad51 / Geminin |
|
27614696 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 | MK-4827能够显著增强辐射对人类肿瘤移植体（p53野生型或p53突变型）的效果[1]。在体内实验中，其耐受良好。单独使用时，在BRCA-1缺陷型移植瘤模型中具有一定功效[2]。 | |
|---|---|---|
| 动物实验 | Animal Models | 雌性裸鼠 |
| Dosages | 25 mg/kg每日两次或50 mg/kg每日一次 | |
| Administration | 口服 | |
| 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 |
化学信息&溶解度
| 分子量 | 320.39 | 分子式 | C19H20N4O |
| CAS号 | 1038915-60-4 | SDF | Download Niraparib (MK-4827) SDF |
| Smiles | C1CC(CNC1)C2=CC=C(C=C2)N3C=C4C=CC=C(C4=N3)C(=O)N | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 64 mg/mL ( (199.75 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Ethanol : 64 mg/mL (199.75 mM) Water : Insoluble |
摩尔浓度计算器 |
|
体内溶解度 现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂 |
动物体内配方计算器 | ||||
实验计算
动物体内配方计算器（澄清溶液）
第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）
mg/kg
g
μL
只
第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）
% DMSO
%
% Tween 80
% ddH2O
%DMSO
%
计算结果：
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于μL DMSO溶液（母液浓度mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；
体内配方配制方法：取μL DMSO母液，加入μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入μL ddH2O，混匀澄清。
体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。
注意：1. 首先保证母液是澄清的；
2.一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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常见问题及建议解决方法
问题 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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