Rucaparib (AG-014699) phosphate

For research use only. Not for use in humans.

目录号:S1098 别名: PF-01367338 中文名称:瑞卡帕布磷酸盐

Rucaparib (AG-014699) phosphate Chemical Structure

CAS No. 459868-92-9

Rucaparib (AG-014699,PF-01367338)是一种PARP抑制剂,无细胞试验中作用于PARP1的Ki为1.4 nM,对其余8个PARP位点也有结合亲和力。Phase 3。

规格 价格 库存 购买数量  
10mM (1mL in DMSO) RMB 1091.92 现货
RMB 980.68 现货
RMB 1730.04 现货
RMB 5483.69 现货
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客户使用Selleck生产的Rucaparib (AG-014699) phosphate发表文献108篇:

产品安全说明书

PARP抑制剂选择性比较

生物活性

产品描述 Rucaparib (AG-014699,PF-01367338)是一种PARP抑制剂,无细胞试验中作用于PARP1的Ki为1.4 nM,对其余8个PARP位点也有结合亲和力。Phase 3。
特性 AG-014699是第一个用于人类癌症疗法的PARP 抑制剂。
靶点
PARP [1]
(Cell-free assay)
1.4 nM(Ki)
体外研究

AG-014699有效抑制纯化的全长人类PARP-1,作用于LoVo和SW620细胞显示出强PARP抑制效果。AG-014699是AG14447的磷酸盐形式,且是第一个和temozolomide联用用于临床实验的PARP抑制剂。[1] AG-014699的辐射增敏性是由于下游NF-κB激活的抑制,及SSB修复抑制。AG-014699可以作用于DNA损伤激活的NF-κB,且克服传统NF-κB抑制剂的毒性,不会损害其他重要的炎症反应。[2]1μM AG-014699作用于D283Med细胞时抑制PARP-1活性达97.1%。[3]在NB-1691, SH-SY-5Y, 和SKNBE(2c)细胞中AG-014699明显增强Topotecan和Temozolomide的细胞毒性。[4]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
BT-474 NHG0ZY5HfW6ldHnvckBCe3OjeR?= NFru[JQxNjFxMT:1NFAwOTByMDDuUS=> NFS1flFqdmirYnn0d{BRSVKSIHHjeIl3cXS7IHH0JJN1[XK2aX7nJINwdmOncn70doF1cW:wIH;mJFUxOCCwTR?= MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTF{OES1OUc,OjVzMki0OVU9N2F-
BT474 NWiye5FyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXjyblRsPTByIH7N NF7nNGIyOOLCk{G1xsBl NHHKemVz\WS3Y3XzJINmdGxiZ4Lve5RpKGmwIITo[UBnd3W{IHzpcoV{KGGwZDDzbYdvcW[rY3HueIx6 MmfzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjVzMki0OVUoRjJ3MUK4OFU2RC:jPh?=
SKBR3 NW[x[3JkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWXFZoJsPTByIH7N NVfFVZk5OTEkgKOxOeKh\A>? Mn;VdoVlfWOnczDj[YxtKGe{b4f0bEBqdiC2aHWg[o92eiCuaX7ld{BidmRic3nncolncWOjboTsfS=> M4nLRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MUK4OFU2Lz5{NUGyPFQ2PTxxYU6=
AU565 NH3KSFVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUS1NFAhdk1? NWD5e3NYOTEkgKOxOeKh\A>? NHLhc3Rz\WS3Y3XzJINmdGxiZ4Lve5RpKGmwIITo[UBnd3W{IHzpcoV{KGGwZDDzbYdvcW[rY3HueIx6 NEfVNJk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUGyPFQ2PSd-MkWxNlg1PTV:L3G+
EFM192A MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVK1NFAhdk1? M17NW|Ex6oDVMUZCpIQ> NFHyc3pz\WS3Y3XzJINmdGxiZ4Lve5RpKGmwIITo[UBnd3W{IHzpcoV{KGGwZDDzbYdvcW[rY3HueIx6 M4j0PVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MUK4OFU2Lz5{NUGyPFQ2PTxxYU6=
MDA-MB-231 Ml3WSpVv[3Srb36gRZN{[Xl? MYKxNE8zOC92MDFOwG0> MUWyOEBp NYGydpB{cW6lcnXhd4V{KHBvQVvUJIxmfmWuczDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6nch?= NX3UWG03RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS0NlAyPTJpPkK0OFIxOTV{PD;hQi=>
MDA-MB-231 M{PtT2NmdGxiVnnhZoltcXS7IFHzd4F6 NVr1c5NOOC5zLUSwJO69VQ>? M3;pN|I1KGh? NXH4WG9PUUN3MPMAjV3jiIlzNz63O:Kh|ryP NIn4bXg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NESyNFE2Oid-MkS0NlAyPTJ:L3G+
MDA-MB-231 MWXBdI9xfG:|aYOgRZN{[Xl? M3HjfVExNzJyL{SwJO69VQ>? M1O3RVI1KGh? NHG0d3dqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5 M1;q[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NEKwNVUzLz5{NESyNFE2OjxxYU6=
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OVTOKO MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoXwTWM2OD12LkG0JOKyKDFwNUOg{txO MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd{OUSwNkc,OjN5Mkm0NFI9N2F-
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TOV21G M3jBZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{GxdWlEPTB;NT6wO{DDuSBzLkOwJO69VQ>? NWT6O2lqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO3Nlk1ODJpPkKzO|I6PDB{PD;hQi=>
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MRC5 NXnscnR4S3m2b4TvfIlkcXS7IHHzd4F6 M{DDVmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJG1TSzViY3XscJMtKEWFNUCgQUA5NjV|IN88UU4> MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjZ3MkexO{c,OjZ4NUK3NVc9N2F-
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... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
BRCA1; 

PubMed: 24085845     


MCF7 cells, MDA-MB-436 parental cells and resistant clones RR-1, RR-5, and RR-6 were treated with DMSO (−) or 1 µM rucaparib (+) for 24 h, and BRCA1 protein levels were assessed by using BRCA1 N- or C-terminal-specific antibodies by Western blot. 

PAR; 

PubMed: 27960087     


MCF-7 cells were pretreated ± Rucaparib (15 µM, 2 hr), then ± Rucaparib (15 µM) or two different doses of β-lap (2.0 or 5.0 µM) for 2 hr. Levels of PAR (PARP hyperactivation) formation were assessed with α-tubulin as loading controls.

24085845 27960087
Growth inhibition assay
Cell viability; 

PubMed: 31119062     


The effect of rucaparib on proliferation of keloid fibroblasts. (A) Keloid cell growth following treatment with rucaparib at various concentration (0, 2, 10, 20 μM) was evaluated by MTT assays. Data are expression as mean standard deviation of percent changes of triplicate optical densities. (B) Rucaparib (20 μM) significantly decreased proliferation of keloid fibroblasts. The combination of rucaparib (20 μM) and triamcinolone (50 μM) showed additive suppressive effect on keloid fibroblasts as compared with rucaparib single therapy. Data are expression as mean standard deviation of percent changes of triplicate optical densities. MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide.

31119062
Immunofluorescence
53BP1; 

PubMed: 23565244     


53BP1 foci was determined by immunofluoresecence microscopy at 24 h following combined treatment with radiation and rucaparib in PC3 and LNCaP cells.

γH2AX; 

PubMed: 23565244     


γH2AX foci was determined by immunofluoresecence microscopy at 24 h following combined treatment with radiation and rucaparib in PC3 and LNCaP cells. 

PAR; 

PubMed: 27515310     


Cells were treated with 20 mM hydrogen peroxide (H2O2) in order to stimulate PARP-1 activity in the presence or absence of the PARP-1 inhibitors rucaparib and olaparib. Poly(ADP-ribose) (PAR) chain synthesis was detected using an anti-PAR monoclonal Alexa Fluor 488-conjugated antibody (green). The nucleus was visualised using the nuclear counterstain DAPI (blue). Representative images obtained from the analysis of anti-PAR staining of SK-N-BE(2c) cells are shown.

α-tubulin; 

PubMed: 30589644     


Representative immunofluorescence images of DMSO-, rucaparib- (Ruca-), and Ola-exposed A549-ERCC1(WT/WT) and A549-ERCC1(–/–) cells. Cells were exposed to 15 μM Ruca or 40 μM Ola during 72 hours. White arrows, CCFs; yellow arrows, micronuclei. Scale bar: 20 μm. 

23565244 27515310 30589644
体内研究 AG-014699无毒,明显增强D384Med移植瘤DNA修复功能蛋白中temozolomide诱导的TGD。药物动力学研究显示在脑组织中也检测到AG-014699,说明AG-014699用于治疗颅内恶性肿瘤具有潜在可能。[3]活体模型(NB1691和SHSY5Y移植瘤)研究显示AG-014699增强temozolomide的抗癌活性,产生彻底且持久的肿瘤衰退现象。[4]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验:[3]
- 合并

激酶实验:

不同浓度(0到1μ)AG-014699作用于5×103D283Med 细胞,与只用DMSO处理5×103D283Med细胞相比,来测定PARP活性抑制率。参考GCLP验证试验的PAR标准曲线,在和NAD+及寡核苷酸(底物和激活剂)温育的6分钟期间,使用10H PAR抗体,通过PAR形成量的免疫检测,在细胞样本中测量最大程度刺激的PARP活性。
细胞实验: [3]
- 合并
  • Cell lines: D425Med, D283Med和D384Med细胞
  • Concentrations: 0.4 μM
  • Incubation Time: 3或5天
  • Method: 髓母细胞瘤细胞系包含D425Med, D283Med,和D384Med细胞,分别按1×103, 3×103,和3×103密度接种在96孔板上。接种24小时(D384Med细胞)或48小时(D283Med和D425Med细胞)后,细胞用不同浓度temozolomide处理。培养3天(D425Med和D384Med细胞)或5天(D283Med细胞)后,通过XTT细胞增殖检测试剂盒检测细胞活力。用DMSO处理的对照组和0.4μ AG-014699处理的实验组的百分比表示细胞生长。计算temozolomide单独使用或者和AG-014699联用时的GI50值。Temozolomide单独使用时的GI50值和与AG-014699联用时的GI50值之比就是趋化因子50(PF50)值。
    (Only for Reference)
动物实验:[3]
- 合并
  • Animal Models: 携带D283Med移植瘤的CD-1裸鼠
  • Dosages: 1 mg/kg
  • Administration: 腹腔注射,每天1次或4次
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 84 mg/mL (199.35 mM)
Water Insoluble
Ethanol Insoluble
体内 从左到右依次将纯溶剂加入产品,现配现用(数据来自Selleck实验检测而非文献):
2% DMSO+30% PEG 300+2% Tween 80+ddH2O
10mg/mL

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 421.36
化学式

C19H18FN3O.H3PO4

CAS号 459868-92-9
储存条件 粉状
溶于溶剂
别名 PF-01367338

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)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
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
计算重置

计算器

摩尔浓度计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系,公式为:

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量

*在配置溶液时,请务必参考Selleck产品标签上、SDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

用本工具协助配置特定浓度的溶液,使用的计算公式为:

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )

  • C1
    V1
    C2
    V2

在配置溶液时,请务必参考Selleck产品标签上、SDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

注:化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04539327 Recruiting Drug: Rucaparib Epithelial Ovarian Cancer|Fallopian Tube Cancer|Primary Peritoneal Cancer Grupo Español de Investigación en Cáncer de Ovario|Clovis Oncology Inc. July 29 2020 --
NCT04179396 Active not recruiting Drug: Rucaparib|Drug: Enzalutamide|Drug: Abiraterone Metastatic Castration Resistant Prostate Cancer Clovis Oncology Inc. December 5 2019 Phase 1
NCT04171700 Recruiting Drug: Rucaparib Solid Tumor Clovis Oncology Inc. November 21 2019 Phase 2
NCT03824704 Terminated Drug: Rucaparib|Drug: Nivolumab Epithelial Ovarian Cancer|Fallopian Tube Cancer|Primary Peritoneal Carcinoma|High Grade Serous Carcinoma|Endometrioid Adenocarcinoma Clovis Oncology Inc.|Bristol-Myers Squibb|Foundation Medicine August 23 2019 Phase 2

技术支持

在订购、运输、储存和使用我们的产品的任何阶段,您遇到的任何问题,均可以通过拨打我们的热线电话400-668-6834,或者技术支持邮箱tech@selleck.cn,直接联系到我们。我们会在24小时内尽快联系您。

操作手册

如果有其他问题,请给我们留言。

  • * 必填项

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID