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ARN-509

现货
Catalog No.
A8364
雄激素受体抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,050.00
现货
5mg
¥ 800.00
现货
10mg
¥ 1,400.00
现货
50mg
¥ 3,500.00
Ship with 10-15 days

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Background

ARN-509, a synthetic biaryl thiohydantoin compound, is a competitive androgen receptor (AR) inhibitor and fully antagonistic to AR overexpression. The IC50 of ARN-509 is 16 nmol/L [1].
AR, included in the steroid receptor superfamily, is important for prostate cell proliferation and male sexual differentiation [2]. AR overexpression is a common and important feature of castration resistant prostate cancer (CRPC) [1].
ARN-509 (1 μmol/L) treatment for 48 hours resulted in increased DNA damage in LNCaP cells, LNCaP-AR cells and VCaP cells. In LNCaP cell line, treatment with ARN-509 (1 μmol/L) resulted in decreased cell survival. Treatment with ARN-509 (1 μmol/L) for 48 hours significantly decreased C-NHEJ–mediated recombination (>60%) in LNCaP cells that had been transfected with V(D)J recombination substrate along with RAG1 and RAG2 expression vectors [3]. ARN-509 showed robust transcriptional and proliferative agonist activity in AR F876L–expressing cells, and promoted AR DNA binding in LNCaP/SRαF876L cells [4].
Orally treated with ARN-509 (10 mg/kg/d) for 17 days, androgendriven luciferase reporter–gene activity in castrate male immunodeficient mice harboring LNCaP/AR-luc xenograft tumors (coexpressing exogenous AR and the AR-dependent reporter ARR2-Pb-luc), was consistently reduced. This indicated that ARN-509 inhibited AR in vivo. ARN-509 made tumors exhibit a decrease in proliferative index and an increase in apoptotic rate [1].
References:
[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.

文献引用

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

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt477.43
Cas No.956104-40-8
FormulaC21H15F4N5O2S
SynonymsARN 509; ARN509
Solubility≥23.85mg/mL in DMSO
Chemical Name4-[7-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide
SDFDownload SDF
Canonical SMILESCNC(=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

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.

生物活性

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

质量控制和MSDS

批次:

化学结构

ARN-509