ARN-509
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.
- 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 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| 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. |
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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 |
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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. |
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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. |
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| Description | ARN-509 is a selective and competitive inhibitor of androgen receptor with an IC50 value of 16 nM. | |||||
| Targets | Androgen Receptor | GABAA receptor | ||||
| IC50 | 16 nM | 3 μM | ||||
Quality Control & MSDS
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Chemical structure
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Related Biological Data
