ARN-509 (Synonyms: ARN 509; ARN509; Apalutamide) |
| Catalog No.GC16840 |
ARN-509 is a synthetic biaryl thiohydantoin compound that inhibits androgen receptor (AR), with an IC50 value of 16nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 956104-40-8
Sample solution is provided at 25 µL, 10mM.
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ARN-509 is a synthetic biaryl thiohydantoin compound that inhibits androgen receptor (AR), with an IC50 value of 16nM[1]. ARN-509 irreversibly binds to the ligand binding domain of the AR with high affinity, induces conformational changes in AR, hinders the translocation of the receptor complex to the nucleus, and thereby prevents its binding to androgen response elements[2]. ARN-509 has been widely used in the related research on prostate cancer treatment[3].
In vitro, ARN-509 treatment (100μM; 24h) significantly inhibited the proliferation of 22Rv1 cells, and suppressed nuclear entry of AR, AR-V7, and phosphorylated AR[4]. Treatment with 10μM ARN-509 significantly inhibited AR signal transduction in LNCaP prostate cancer cell lines, resulting in reduced cell proliferation[1].
In vivo, ARN-509 treatment through oral gavage at a dose of 30mg/kg/day for 60 weeks, which significantly reduced the incidence of prostate cancer induced by N-methyl-N-nitrosourea in male Wistar rats[5]. In the LNCaP/AR castration-resistant prostate cancer (CRPC) mouse model, an oral administration dose of 10mg/kg/day of ARN-509 can significantly inhibit tumor regression[6]. In genetically engineered mouse prostate cancer (GEM-PCa) models, four weeks of oral treatment with ARN-509 (30mg/kg/day) significantly reduced tumor burden by 33.5% and increased PI3K-AKT signaling[7].
References:
[1]Clegg N J, Wongvipat J, Joseph J D, et al. ARN-509: a novel antiandrogen for prostate cancer treatment[J]. Cancer research, 2012, 72(6): 1494-1503.
[2]Smith M R, Antonarakis E S, Ryan C J, et al. Phase 2 study of the safety and antitumor activity of apalutamide (ARN-509), a potent androgen receptor antagonist, in the high-risk nonmetastatic castration-resistant prostate cancer cohort[J]. European urology, 2016, 70(6): 963-970.
[3]Smith M R, Antonarakis E S, Ryan C J, et al. ARN-509 in men with high risk non-metastatic castration-resistant prostate cancer[J]. Annals of Oncology, 2012, 23: ix303.
[4]Koukourakis M I, Kakouratos C, Kalamida D, et al. Comparison of the effect of the antiandrogen apalutamide (ARN-509) versus bicalutamide on the androgen receptor pathway in prostate cancer cell lines[J]. Anti-cancer drugs, 2018, 29(4): 323-333.
[5]Murillo G, Peng X, Muzzio M, et al. Exceptional activity of ARN-509 (apalutamide) in prostate cancer prevention in rats[J]. Cancer Research, 2019, 79(13_Supplement): 2730-2730.
[6]Hager J H, Smith N D, Bischoff E, et al. Effect of the novel anti-androgen ARN-509 on response and seizure in castration-resistant prostate cancer models[J]. Journal of Clinical Oncology, 2011, 29(7_suppl): 28-28.
[7]Velasco M A D, Nozawa M, Kura Y, et al. Apalutamide (ARN-509) demonstrates therapeutic efficacy in genetically engineered mouse models of Pten-deficient prostate cancer[J]. Cancer Research, 2018, 78(13_Supplement): 3737-3737.
| Cell experiment [1]: | |
Cell lines | 22Rv1 cells |
Preparation Method | 2.5×10322Rv1 cells were inoculated in each well on a 96-well plate and incubated for 24 hours to allow the cells to attach to the well surface. Then, the cells were exposed to ARN-509 (10, 50, and 100μM; 24h) and Testosterone (10μmol/L; 24h). The effects on cell viability were tested when the ARN-509 and Testosterone were continuously present in the culture medium. To assess cell viability, 10%v/v AlamarBlue was added to each well. As a negative control (background measurement), ARN-509 was not contained in the culture medium. Vitamin C (5μl/well) was used as the positive control to completely reduce rizulin. Seven hours later, the relative fluorescence (in RFU: fluorescence per well minus background fluorescence) was measured using the microplate reader. Measure every other day from day 0 (24 hours after sowing) to day 6. The experiments were conducted under normal hypoxia and 1% hypoxia conditions. |
Reaction Conditions | 10, 50, and 100μM; 24h |
Applications | ARN-509 significantly inhibited the viability of 22Rv1 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | SHO male mice |
Preparation Method | The in vivo xenotransplantation experiment was conducted in male SHO mice. Mice had their testicles removed under isoflurane anesthesia and were given a recovery time of 7 to 10 days. LNCaP/AR (cs) cells were suspended in 50% RPMI and 50% Matrigel. 3×106 cells were injected into each xenograft, with a volume of 100μL. Observe the animals every week until the tumor grows significantly. Forty to 60 days after injection, the animals were randomly divided into cohorts with equal average tumor burden and range (150-250mm3). In all LNCaP/AR (cs) xenotransplantation studies, ARN-509 (30mg/kg) and enzalutamide active pharmaceutical ingredients were prepared in 18% PEG-400, 1% Tween-80 and 1% povidone, and in 15% vitamin E-TPGS and 65% 0.5% w/v CMC solution, all compounds were administered by oral gavage daily. After daily administration of ARN-509 for 60 days, the tumor growth in mice was analyzed. |
Dosage form | 30mg/kg/day for 60 days; p.o. |
Applications | ARN-509 treatment significantly suppressed tumor growth, and increased the survival rate of mice. |
References: | |
| Cas No. | 956104-40-8 | SDF | |
| Synonyms | ARN 509; ARN509; Apalutamide | ||
| 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 | ||
| 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 | ||
| Formula | C21H15F4N5O2S | M.Wt | 477.43 |
| Solubility | ≥ 23.85mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.0945 mL | 10.4727 mL | 20.9455 mL |
| 5 mM | 418.9 μL | 2.0945 mL | 4.1891 mL |
| 10 mM | 209.5 μL | 1.0473 mL | 2.0945 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 34 reference(s) in Google Scholar.)
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