1. Others
  2. Androgen Receptor

ARN-509 (Synonyms: Apalutamide)

Cat. No.: HY-16060 Purity: 99.23%
Handling Instructions

ARN-509 is a potent and competitive androgen receptor (AR) antagonist, binds AR with IC50 of 16 nM.

For research use only. We do not sell to patients.
ARN-509 Chemical Structure

ARN-509 Chemical Structure

CAS No. : 956104-40-8

Size Price Stock Quantity
Free sample   Apply now  
10 mM * 1 mL in DMSO $77 In-stock
5 mg $70 In-stock
10 mg $120 In-stock
50 mg $350 In-stock
100 mg $550 In-stock
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

Customer Review

Top Publications Citing Use of Products
  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

ARN-509 is a potent and competitive androgen receptor (AR) antagonist, binds AR with IC50 of 16 nM.

IC50 & Target

IC50: 16 nM (Androgen receptor)[1]

In Vitro

ARN-509 also exhibits low micromolar affinity (IC50 3 μM) for the GABAA receptor in radioligand binding-assays and thus may potentially antagonize GABAA at therapeutic dose levels[1]. Apalutamide is a potent androgen receptor (AR) antagonist that targets the AR ligand-binding domain and prevents AR nuclear translocation, DNA binding, and transcription of AR gene targets[2].

In Vivo

ARN-509 exhibits low systemic clearance, high oral bioavailability and long plasma half-life in both mouse and dog, supporting once-daily oral dosing. Consistent with its long terminal-half-life, ARN-509 steady-state plasma-levels increases in repeat-dose studies, resulting in high C24hr levels and low peak:trough ratios (ratio:2.5). Castrate male mice bearing LNCaP/AR xenograft tumors are treated with either ARN-509 at doses of 1, 10 or 30 mg/kg/day. Thirteen of 20 ARN-509 (30 mg/kg/day)-treated animals exhibit >50% reduction in tumor-volume at day 28 versus 3 of 19 MDV3100 (30 mg/kg/day)-treated mice[1].

Clinical Trial
Sponsor Condition Start Date Phase
Aragon Pharmaceuticals Inc Hormone refractory prostate cancer 2013-10-31 Phase 3
Aragon Pharmaceuticals Inc Hormone dependent prostate cancer 2013-02-28 Phase 2
Aragon Pharmaceuticals Inc Hormone refractory prostate cancer 2010-07-31 Phase 2
Aragon Pharmaceuticals Inc 2013-03-31 Phase 1
Aragon Pharmaceuticals Inc; Johnson & Johnson Hormone refractory prostate cancer 2013-02-28 Phase 1
References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 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
Kinase Assay
[1]

Competitor assay kits (green) are used to determine relative in vitro binding affinities of ARN-509 for the rat AR ligand binding domain (LBD), human progesterone receptor (PR) LBD, and full-length human estrogen receptor-alpha (ERα) and human glucocorticoid receptor (GR). Each hormone dose is performed in triplicate, relative error is calculated from the standard error of the mean (SEM), and binding curves are fit using a single binding site competition model (Prism statistical analysis software package) with R2>0.8. Experiments are conducted multiple times with SEM<0.3 log units from the average logIC50 value. Ki values are calculated as averages across experiments with SEM, and binding affinities are reported as a percentage relative to the tight-binding ligand control for that receptor[1].

Cell Assay
[1]

ARN-509 is dissolved in DMSO and stored, and then diluted with appropriate medium before use[1].

Trypsinized VCaP cells are adjusted to a concentration of 100,000 cells per mL in phenol-red-free RPMI 1640 (with 5% CSS), and dispensed in 16 µL aliquots into CellBIND 384 well plates. Cells are incubated for 48 hours, after which ligand is added in a 16 µL volume to the RPMI culture medium. For the antagonist mode assay, the ligands are diluted in culture medium also containing 30 pM R1881. After 7 days’ incubation, 16 µL of CellTiter-Glo Luminescent Cell Viability Assay is added and Relative Luminescence Units (RLUs) measured[1].

Animal Administration
[1]

ARN-509 is prepared in 18% PEG-400, 1% Tween-80 and 1% povidone, and is formulated for dosing in 15% Vitamin E-TPGS and 65% of a 0.5% w/v CMC solution in 20 mM citrate buffer (pH 4.0) (Mice)[1].

Mice[1]
In vivo xenograft experiments to determine anti-tumor response are carried out in SHO SCID male mice. Mice are orchiectomized under isoflorane anesthesia and are given 2-3 days to recover prior to tumor cell injection. LNCaP/AR(cs) cells are suspended in 50% RPMI, 50% Matrigel, and 5×106 cells/xenograft are injected in a volume of 100 μL. Animals are observed weekly until tumor growth is apparent. From 24 d post-injection, tumors are measured weekly, and after 40-60 days post-injection, animals are randomized into cohorts of equivalent mean (150-250 mm3) and range tumor burden. All compounds (e.g., ARN-509, 30 mg/kg per day) are administered daily by oral gavage. Statistical analyses are performed using Graphpad Prism.

References
M.Wt

477.43

Formula

C₂₁H₁₅F₄N₅O₂S

CAS No.

956104-40-8

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

Purity: 99.23%

Inquiry Online

Your information is safe with us. * Required Fields.

Product name

 

Salutation

Applicant name *

 

Email address *

Phone number

 

Organization name *

Country *

 

Requested quantity *

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
ARN-509
Cat. No.:
HY-16060
Quantity: