Rucaparib (AG-014699,PF-01367338) phosphate
目录号：S1098
Molecular Weight(MW): 421.36
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。
客户使用该产品的8个实验数据：
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Representative images for RAD51 and γH2AX foci formation, surrogate DSB markers, in stable shK-H or shSCR 231 cells after rucaparib or vehicle (0.01% DMSO) treatment for 24 hours. DAPI-stained cell nuclei. Scale bars, 10 μm.
Clin Cancer Res, 2018, doi:10.1158/1078-0432.CCR-17-1118. Rucaparib (AG-014699,PF-01367338) phosphate purchased from Selleck.
MDA-MB-231 cells were inoculated into mammary fad pad of nude mice, and the mice with established tumors were treated with olaparib or rucaparib. Tumors were then isolated to evaluate PD-L1 expression by IHC staining (C). Black arrowheads indicate the detected PD-L1 signals. Scale bar, 50 μm.
Clin Cancer Res, 2017, 23(14):3711-3720. Rucaparib (AG-014699,PF-01367338) phosphate purchased from Selleck.
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For anchorage dependent clonogenic assays, HER2+ breast cancer BT474 cells were seeded at low density in 6-well plates and allowed to adhere overnight. The next day, olaparib and rucaparib were added at the indicated concentrations. Media and drugs were replenished every three days. After 10-15 days, depending on cell proliferation rate, cells were fixed and stained with crystal violet. Images and graphs indicate the results compared to control condition. Data are mean ± S.D. n.s.: non-significant, ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.
Eur J Cancer 2014 50(15), 2725-34. Rucaparib (AG-014699,PF-01367338) phosphate purchased from Selleck.
Total cell extracts of BT-474 cells treated with increasing concentrations of olaparib or rucaparib were subjected to western blot analysis for PARP-1 and poly ADP-ribose (PAR) expression. β-tubulin was used as loading control. Representative images from two separate experiments are shown.
Eur J Cancer 2014 50(15), 2725-34. Rucaparib (AG-014699,PF-01367338) phosphate purchased from Selleck.
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Three sensitive and three resistant cell lines were treated for 24 h with 0.02% DMSO (negative control) or 10 uM rucaparib. Serving as positive control were cells fixed 30 min after exposure to 2 Gy IR. Image acquisition was performed with a confocal microscope (Leica TCS SP2) using the 100X objective and a 2X optical zoom and oil immersion. Red: γH2AX foci. Green: RAD51 foci. *P < 0.05 **P < 0.01 ***P < 0.001. Fluorescence microscopy images of DAPI-stained rucaparib-sensitive (HN4) and rucaparib-resistant (SAS) HNC cell lines treated with DMSO, 2 Gy or 10 uM rucaparib for 24 h.
Oral Oncol 2014 50(9), 825-31. Rucaparib (AG-014699,PF-01367338) phosphate purchased from Selleck.
purified PARP-1 and His-XPA were incubated alone ( lane 7 ), with activated PARP-1 (addition of activated DNA and NAD＋, lane 8 ), or in the presence of the PARP inhibitor AG-014699 (lane 9 ). Following the various treatments, His-XPA was pulled down ( IP ) from each sample using cobalt-conjugated magnetic beads.
J Biol Chem 2012 287, 39824-33. Rucaparib (AG-014699,PF-01367338) phosphate purchased from Selleck.
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Antitumor effects of transfecting of INPP4B gene combined with PARP inhibitor treatment on PC3 cells. (A) The change of cell number and shape under the microscope. (B) The viability of PC3 cells measured using CCK-8. (C) The cell cycle phase distribution of PC3 detected by flow cytometry. (D) Apoptosis of PC3 cells detected using annexin V-FITC/PI staining. (Asterisks denote statistical significance between Lenti-INPP4B+PARP inhibitor and Lenti-INPP4B and PARP inhibitor treatment, *P<0.05).
Urol Oncol 2014 32(5), 720-6. Rucaparib (AG-014699,PF-01367338) phosphate purchased from Selleck.
in vivo suppression of PAR formation by the PARP inhibitor AG-014699 upon induction of DNA damage
Primary human lung fibroblast cells (MRC-5) were pre-treated with the indicated concentration of the PARP inhibitor AG-014699 for two hours. Oxidative DNA damage was induced by 500 µM H2O2 for 10 min and cellular PARP activity was measured by immuno-staining of poly(ADP)-ribose (PAR) (right panels). The in vivo effect of PARP inhibition was compared to cells without DNA damage induction and inhibitor (control) and H2O2-treated cells without inhibitor.
Average nuclear PAR staining intensities of more than 50 cells were statistically analysed by Kruskal-Wallis and the post-hoc Dunn’s Multiple Comparison tests (left panel). Asterisks indicate highly significant (p<1%) differences to H2O2-treated cells without PARP inhibitor. Thick horizontal bars mark medians and error bars the interquartile range.Dr. David Schrmann from University of Base. Rucaparib (AG-014699,PF-01367338) phosphate purchased from Selleck.
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。 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 特性 | AG-014699是第一个用于人类癌症疗法的PARP 抑制剂。 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 靶点 |
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| 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] |
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| Cell Data |
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| 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] |
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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。 |
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| 细胞实验： [3] |
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| 动物实验：[3] |
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溶解度 (25°C)
| 体外 | DMSO | 84 mg/mL (199.35 mM) |
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| 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 |
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| 化学式 | C19H18FN3O.H3PO4 |
| CAS号 | 459868-92-9 |
| 稳定性 | powder |
| in solvent | |
| 别名 | N/A |
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 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)
摩尔浓度计算公式
*在配置溶液时，请务必参考Selleck产品标签上、MSDS / 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
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 )
在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。.
分子量计算器
通过输入化合物的化学式来计算其分子量：
注：化学分子式大小写敏感。C10H16N2O2 c10h16n2o2
摩尔浓度计算器
临床试验信息
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT03694262 | Not yet recruiting | Endometrial Cancer | Medical College of Wisconsin | February 1 2019 | Phase 2 |
| NCT03559049 | Not yet recruiting | Stage IV Non-small Cell Lung Cancer | University of Michigan Cancer Center|Merck Sharp & Dohme Corp.|Clovis Oncology Inc. | January 2019 | Phase 1|Phase 2 |
| NCT03617679 | Not yet recruiting | Metastatic Endometrial Cancer | University of Colorado Denver|Clovis Oncology Inc. | December 2018 | Phase 2 |
| NCT03639935 | Not yet recruiting | Biliary Tract Cancer | University of Michigan Cancer Center|Dana-Farber Cancer Institute|Vanderbilt University Medical Center | November 2018 | Phase 2 |
| NCT03654833 | Not yet recruiting | Mesothelioma Malignant | University of Leicester|British Lung Foundation|Clovis Oncology Inc.|Eli Lilly and Company|Merck Sharp & Dohme Corp.|BerGenBio ASA|Roche Pharma AG|University Hospitals Leicester|The Christie NHS Foundation Trust | October 1 2018 | Phase 2 |
| NCT03413995 | Recruiting | Prostate Cancer Metastatic | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | September 10 2018 | Phase 2 |
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