ARN-509
![mRNA synthesis](/media/diy/images/page/figure1-mrna.png)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
![Tyramine Signal Amplification (TSA)](/media/diy/images/page/figure2-01.png)
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
![screening library](/media/diy/images/page/figure3-01.png)
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
![Cell Counting Kit-8 (CCK-8)](/media/diy/images/page/CCK-8.jpg)
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
![SYBR Safe DNA Gel Stain](/media/diy/images/page/SYBR Safe DNA Gel Stain.png)
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
![Inhibitor Cocktails](/media/diy/images/page/Inhibitor Cocktails.jpg)
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
ARN-509,合成的联芳硫代乙内酰脲(biaryl thiohydantoin)化合物,是一种竞争性的雄激素受体(AR)抑制剂,完全拮抗AR的过表达。ARN-509的IC50值为16 nmol/L[1]。
AR属于类固醇受体超家族,在前列腺细胞的增殖和男性性分化方面具有重要作用[2]。AR的过表达是去势抵抗性前列腺癌(CRPC)一个共同的和重要的特征[1]。
在LNCaP细胞、LNCaP-AR细胞和VCaP细胞中,ARN-509(1 μmol/L)处理48小时可导致DNA损伤的增加。在LNCaP细胞系中,ARN-509(1 μmol/L)减少细胞存活。在转染V(D)J重组底物,以及RAG1和RAG2表达载体的LNCaP细胞中,ARN-509(1 μmol/L)处理48小时显著减少C-NHEJ介导的重组(>60%)[3]。在表达AR F876L的细胞中,ARN-509显示出强烈的转录和增殖的激动活性。在LNCaP/SRα F876L细胞中,ARN-509促进AR与DNA的结合[4]。
在携带LNCaP/AR-luc异种移植肿瘤(共表达外源性AR和AR依赖性报告基因ARR2-Pb-luc)的去势雄性免疫缺陷小鼠中,ARN-509(10 mg/kg/d)口服给药17天后持续减少雄激素驱动的荧光素酶报告基因的活性。这表明ARN-509抑制AR。ARN-509诱导肿瘤增殖指数的降低和凋亡率的增加[1]。
参考文献:
[1]. Nicola J. Clegg, John Wongvipat, James D. Joseph, et al. ARN-509: A Novel Antiandrogen for Prostate Cancer Treatment. Therapeutics, Targets & Chemical Biology, 2012, 72(6): 1494-1503.
[2]. Shuyuan Yeh and Chawnshang Chang. Cloning and characterization of a specific coactivator, ARA70, for the androgen receptor in human prostate cells. Proc. Natl. Acad. Sci., 1996, 93: 5517-5521.
[3]. William R. Polkinghorn, Joel S. Parker, Man X. Lee, et al. Androgen Receptor Signaling Regulates DNA Repair in Prostate Cancers. Cancer Discovery, 2013, 3(11):1245-53.
[4]. James D. Joseph, Nhin Lu, Jing Qian, et al. A Clinically Relevant Androgen Receptor Mutation Confers Resistance to Second-Generation Antiandrogens Enzalutamide and ARN-509. Cancer Discovery, 2013, 3(9):1020-9.
- 1. Bao D, Cheng C, et al. "Regulation of p53wt glioma cell proliferation by androgen receptor-mediated inhibition of small VCP/p97-interacting protein expression."Oncotarget. 2017 Apr 4;8(14):23142-23154. PMID:28423563
- 2. Sun J, Wang D, et al. "Androgen Receptor Regulates the Growth of Neuroblastoma Cells in vitro and in vivo." Front Neurosci. 2017 Mar 7;11:116. PMID:28326012
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 477.43 |
Cas No. | 956104-40-8 |
Formula | C21H15F4N5O2S |
Synonyms | ARN 509; ARN509 |
Solubility | ≥23.85 mg/mL in DMSO; insoluble in H2O; ≥7.33 mg/mL in EtOH |
Chemical Name | 4-[7-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide |
SDF | Download SDF |
Canonical SMILES | CNC(=O)C1=C(C=C(C=C1)N2C(=S)N(C(=O)C23CCC3)C4=CN=C(C(=C4)C(F)(F)F)C#N)F |
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 |
LNCaP、LNCaP-AR和VCaP细胞 |
制备方法 |
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 °C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 °C可放置数月。 |
反应条件 |
1 μM;48小时 |
实验结果 |
在LNCaP、LNCaP-AR和VCaP细胞中,ARN-509增加DNA损伤。 在LNCaP细胞系中,ARN-509降低细胞存活率。 此外,在转染V(D)J重组底物以及RAG1和RAG2表达载体的LNCaP细胞中,ARN-509显著降低C-NHEJ介导的重组 (> 60%)。 |
动物实验 [2]: | |
动物模型 |
携带LNCaP/AR-luc异种移植瘤的去势雄性免疫缺陷小鼠 |
给药剂量 |
10 mg/kg/d;口服给药;持续17天 |
实验结果 |
在携带LNCaP/AR-luc异种移植瘤的去势雄性免疫缺陷小鼠中,ARN-509(10 mg/kg/d,口服给药,持续17天)持续降低雄激素介导的荧光素酶报告基因活性。 此外,ARN-509减少肿瘤增殖指数并增加肿瘤凋亡率。 |
其它注意事项 |
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]. William R. Polkinghorn, Joel S. Parker, Man X. Lee, et al. Androgen Receptor Signaling Regulates DNA Repair in Prostate Cancers. Cancer Discovery, 2013, 3(11):1245-53. [2]. Nicola J. Clegg, John Wongvipat, James D. Joseph, et al. ARN-509: A Novel Antiandrogen for Prostate Cancer Treatment. Therapeutics, Targets & Chemical Biology, 2012, 72(6): 1494-1503. |
描述 | ARN-509是一种选择性的和竞争性的雄激素受体抑制剂,IC50值为16 nM。 | |||||
靶点 | Androgen Receptor | GABAA receptor | ||||
IC50 | 16 nM | 3 μM |
质量控制和MSDS
- 批次:
化学结构
![ARN-509](http://www.apexbt.com/media/diy/images/struct/A8364.png)
相关生物数据
![ARN-509 ARN-509](http://www.apexbt.com/media/diy/images/wb/A8364_1.jpg)
相关生物数据
![ARN-509 ARN-509](http://www.apexbt.com/media/diy/images/wb/A8364_2.jpg)