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Rucaparib (free base)

现货
Catalog No.
A8893
PARP抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 800.00
现货
5mg
¥ 750.00
现货
10mg
¥ 1,300.00
现货
50mg
¥ 3,500.00
现货
200mg
¥ 8,500.00
Ship with 10-15 days

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Background

Rucaparib, also named as AG-014699 or PF-01367338, is a poly (ADP ribose) polymerase (PARP) inhibitor. PARP is a DNA damage-activated nuclear enzyme that has a key signaling role in the base excision repair pathway. So, rucaparib has been also found to be most effective in cells deficient in DNA repair, where the cells deficient are caused by exposure to genotoxic agents, such as irradiation produces DNA damage and its toxicity is augmented when the DNA repair is impaired. Increased radiosensitivity in presence of rucaparib was associated with persistent DNA breaks as determined by gamma-H2AX and p53BP1 foci. Rucaparib radiosensitizes prostate cancer cells, most effectively those that are PTEN-deficient and are expressing ETS gene fusion proteins, which inhibits NHEJ DNA repair.

References

Ruth Plummer, Paul Lorigan, Neil Steven, Lucy Scott, Mark R. Middleton, Richard H. Wilson, Evan Mulligan, Nicola Curtin, Diane Wang, Raz Dewji, Antonello Abbattista, Jorge Gallo, Hilary Calvert. A phase II study of the potent PARP inhibitor, Rucaparib (PF-01367338, AG014699), with temozolomide in patients with metastatic melanoma demonstrating evidence of chemopotentiation.

Payel Chatterjee, Gaurav Choudhary, Warren D. Heston, Eric A. Klein, Alex Almasan. The PARP inhibitor rucaparib radiosensitizes prostate cancer cells, most effectively those that are PTEN-deficient and are expressing ETS gene fusion proteins, which inhibit NHEJ DNA repair. Cancer Research. 2012. 72: B27.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt323.36
Cas No.283173-50-2
FormulaC19H18FN3O
Solubility≥16.15mg/mL in DMSO
Chemical Name8-fluoro-2-(4-((methylamino)methyl)phenyl)-4,5-dihydro-1H-azepino[5,4,3-cd]indol-6(3H)-one
SDFDownload SDF
Canonical SMILESFC1=CC2=C3C(CCNC2=O)=C(C4=CC=C(CNC)C=C4)NC3=C1
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验: [1]

细胞系

犬肾MDCKII细胞系

制备方法

该化合物在DMSO中的溶解度大于10 mM,若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

8h;5 μM

实验结果

在过表达人(h)ABCB1的MDCKII亲本细胞系中,rucaparib的顶端和基底外侧定向易位是相同的。用ABCB1抑制剂zosuquidar处理细胞降低顶端定向转运,这可能是由于特异性抑制基底外侧的未鉴定的rucaparib摄取转运蛋白或抑制内源性犬ABCB1。结果表明,rucaparib是ABCB1的转运底物。

动物实验: [1]

动物模型

>99%FVB遗传背景的雌性WT Abcb1a/1b小鼠

给药剂量

10 mg/kg,口服

实验结果

在野生型(WT)和单一及组合Abcg2和Abcb1a/1b敲除小鼠中,我们分析了口服10 mg/kg的rucaparib对于Abcg2和Abcb1a/1b活性的单独和共同作用的效果。口服10 mg/kg的rucaparib后,由于缺乏Abcg2和Abcb1a/1b,1和24小时的rucaparib的体内口服可用性(血浆AUC0-1和AUC0-24)和脑含量增加。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1] Durmus S, Sparidans R W, van Esch A, et al. Breast Cancer Resistance Protein (BCRP/ABCG2) and P-glycoprotein (P-GP/ABCB1) Restrict Oral Availability and Brain Accumulation of the PARP Inhibitor Rucaparib (AG-014699)[J]. Pharmaceutical research, 2014: 1-10.

生物活性

Rucaparib(AG-014699、PF-01367338)是一种有效的PARP抑制剂,Ki值为1.4 nM。.
靶点 PARP          
IC50 1.4 nM (Ki)          

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