Rucaparib (AG-014699,PF-01367338)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Rucaparib,又名AG-014699或PF-01367338,是一种PARP抑制剂。PARP是一种由DNA损伤激活的核酶,在碱基切除修复信号通路中具有关键的信号作用。因此,研究认为rucaparib在DNA修复功能缺陷的细胞中最为有效。这些细胞缺陷可通过暴露于基因毒性剂而引起。例如,放射造成的DNA损伤,其毒性又会因为DNA修复缺陷而加剧。通过gamma-H2AX和p53BP1 foci证明,rucaparib存在条件下辐射敏感性的增加与持续性的DNA断裂相关。Rucaparib对前列腺癌细胞有辐射增敏作用,尤其是对PTEN缺陷和表达ETS基因融合蛋白的细胞,其抑制NHEJ DNA修复。
参考文献:
[1] 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.
[2] 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.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 421.36 |
Cas No. | 459868-92-9 |
Formula | C19H18FN3O·H3PO4 |
Synonyms | Rucaparib phosphate,AG-14699,AG 014699 |
Solubility | ≥21.08 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O |
Chemical Name | 8-fluoro-2-(4-((methylamino)methyl)phenyl)-4,5-dihydro-1H-azepino[5,4,3-cd]indol-6(3H)-one phosphate |
SDF | Download SDF |
Canonical SMILES | OP(O)(O)=O.FC1=CC2=C3C(CCNC2=O)=C(C4=CC=C(CNC)C=C4)NC3=C1 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
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 |
8 h,5 μM |
实验结果 |
在MDCKII亲本细胞系中,其过表达人(h)ABCB1,rucaparib的顶端和基底侧定向的易位是相同的。ABCB1抑制剂zosuquidar导致细胞顶端定向转运的轻微降低,这可能是由于在基底外侧的未鉴定的rucaparib摄取转运蛋白的特异性抑制或内源性ABCB1的抑制。结果表明,rucaparib是ABCB1的转运底物。 |
动物实验[1]: | |
动物模型 |
含有>99%的遗传背景的雌性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 |
请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。 |
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. |
Rucaparib (AG-014699,PF-01367338) 是一种PARP1抑制剂,Ki值为1.4 nM。. | ||||||
靶点 | PARP | |||||
IC50 | 1.4 nM (Ki) |
质量控制和MSDS
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