Rucaparib (AG-014699,PF-01367338) phosphate
製品コードS1098
分子量(MW)：421.36
Rucaparib (AG-014699, PF-01367338) is an inhibitor of PARP with Ki of 1.4 nM for PARP1 in a cell-free assay, also showing binding affinity to eight other PARP domains. Phase 3.
カスタマーフィードバック(8)
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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.
製品安全説明書
PARP阻害剤の選択性比較
生物活性
| 製品説明 | Rucaparib (AG-014699, PF-01367338) is an inhibitor of PARP with Ki of 1.4 nM for PARP1 in a cell-free assay, also showing binding affinity to eight other PARP domains. Phase 3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 特性 | The first PARP inhibitor used in clinical trials combined with temozolomide. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ターゲット |
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| 体外試験 |
Rucaparib is a potent inhibitor of purified full-length human PARP-1 and shows higher inhibition of cellular PARP in LoVo and SW620 cells. Besides, Rucaparib binds detectably to eight other PARP domains, including PARP2, 3, 4, 10, 15, 16, TNKS1 and TNKS2. [1] [2] The radio-sensitization by Rucaparib is due to downstream inhibition of activation of NF-κB, and is independent of SSB repair inhibition. Rucaparib could target NF-κB activated by DNA damage and overcome toxicity observed with classical NF-κB inhibitors without compromising other vital inflammatory functions. [3] Rucaparib inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilised D283Med cells. [4] |
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| 細胞データ |
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| 体内試験 | Rucaparib is not toxic but significantly enhances temozolomide-induced TGD in the DNA repair protein-competent D384Med xenografts. Pharmacokinetics studies also show that Rucaparib is detected in the brain tissue, which indicates that Rucaparib has potential in intra-cranial malignancy therapy. [4] Rucaparib significantly potentiates the cytotoxicity of topotecan and temozolomide in NB-1691, SH-SY-5Y, and SKNBE (2c) cells. Rucaparib enhances the antitumor activity of temozolomide and indicates complete and sustained tumor regression in NB1691 and SHSY5Y xenografts. [5] |
お薦めの試験操作（参考用のみ）
| キナーゼ試験：[1] |
+ 展開
Ki Determination: Inhibition of human full-length recombinant PARP-1 by [32P]NAD+ incorporation is measured. The [32P]ADP-ribose incorporated into acid insoluble material is quantified using a PhosphorImager. Ki is calculated by nonlinear regression analysis. |
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| 細胞試験： [4] |
+ 展開
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| 動物試験：[4] |
+ 展開
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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 |
左から（NMPから）右の順に溶剤を製品に加えます(文献ではなく、Selleckの実験によるデータ): 2% DMSO+30% PEG 300+2% Tween 80+ddH2O 混合させたのち直ちに使用することを推奨します。 |
10mg/mL |
* 溶解度測定はSelleck技術部門によって行われており、その他文献に示されている溶解度と差異がある可能性がありますが、同一ロットの生産工程で起きる正常な現象ですからご安心ください。
化学情報
| 分子量 | 421.36 |
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| 化学式 | C19H18FN3O.H3PO4 |
| CAS No. | 459868-92-9 |
| 保管 | 粉 |
| in solvent | |
| 別名 | N/A |
便利ツール
モル濃度計算器
求めたい質量、体積または濃度を計算してください。
質量 (g) = 濃度 (mol/L) x 体積 (L) x 分子量 (g/mol)
モル濃度計算器方程式
*貯蔵液を準備するとき、常に、オンであるとわかる製品のバッチに特有の分子量を使って、を通してラベルとMSDS/COA（製品ページで利用可能な）。
希釈計算器
貯蔵液を準備するために必要な希釈率を計算してください。Selleck希釈計算器は、以下の方程式に基づきます：
開始濃度 x 開始体積 = 最終濃度 x 最終体積
希釈の計算式
この方程式は、一般に略語を使われます：C1V1 = C2V2 ( 入力 出力 )
常に貯蔵液を準備するとき、小びんラベルとMSDS/COA（オンラインで利用できる）で見つかる製品のバッチに特有の分子量を使ってください。
分子量计算器
そのモル質量と元素組成を計算するために、合成物の化学式を入力してください：
チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2
モル濃度計算器
臨床試験
| 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 |
技術サポート
ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。
他に質問がある場合は、お気軽にお問い合わせください。
