ARN-509
(Synonyms: 阿帕鲁胺,ARN 509; ARN509) 目录号 : GC16840
An androgen receptor antagonist
Cas No.:956104-40-8
Sample solution is provided at 25 µL, 10mM.
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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.
| Cell experiment [1]: | |
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Cell lines |
LNCaP, LNCaP-AR and VCaP cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
|
Reacting condition |
1 μM; 48 hrs |
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Applications |
In LNCaP, LNCaP-AR and VCaP cells, ARN-509 increased DNA damage. In LNCaP cell line, ARN-509 decreased cell survival. In addition, ARN-509 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. |
| Animal experiment [2]: | |
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Animal models |
Castrate male immunodeficient mice harboring LNCaP/AR-luc xenograft tumors |
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Dosage form |
10 mg/kg/d; p.o.; for 17 days |
|
Applications |
In castrate male immunodeficient mice harboring LNCaP/AR-luc xenograft tumors, the 17-day Oral treatment with ARN-509 (10 mg/kg/d) consistently reduced androgen-driven luciferase reporter-gene activity. In addition, ARN-509 decreased the proliferative index and increased the apoptotic rate of tumors, respectively. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
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. | |
| Cas No. | 956104-40-8 | SDF | |
| 别名 | 阿帕鲁胺,ARN 509; ARN509 | ||
| 化学名 | 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 | ||
| 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 | ||
| 分子式 | C21H15F4N5O2S | 分子量 | 477.43 |
| 溶解度 | ≥ 23.85mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.0945 mL | 10.4727 mL | 20.9455 mL |
| 5 mM | 0.4189 mL | 2.0945 mL | 4.1891 mL |
| 10 mM | 0.2095 mL | 1.0473 mL | 2.0945 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet