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  2. Androgen Receptor

ARN-509 (Synonyms: Apalutamide)

Cat. No.: HY-16060 Purity: 99.23%
Data Sheet SDS 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

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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
NCT Number Sponsor Condition Start Date Phase
NCT03124433 Singapore General Hospital Cancer of the Prostate May 1, 2017 Phase 2
NCT02811809 Robert J Amato|Janssen Scientific Affairs, LLC|The University of Texas Health Science Center, Houston Prostate Cancer July 1, 2017 Phase 2
NCT03173859 University of Athens Prostatic Neoplasms, Castration-Resistant July 1, 2017 Phase 2
NCT02906605 Janssen Research & Development, LLC Prostatic Neoplasms, Castration-Resistant October 2016 Phase 2
NCT03088124 Institut Paoli-Calmettes|Janssen-Cilag Ltd. Low Risk Prostate Cancer April 28, 2017 Phase 2
NCT02489318 Aragon Pharmaceuticals, Inc. Prostate Cancer November 27, 2015 Phase 3
NCT02867020 Latin American Cooperative Oncology Group|Janssen Pharmaceuticals Prostate Cancer January 2017 Phase 2
NCT02789878 Instituto do Cancer do Estado de São Paulo|Janssen, LP Prostate Cancer June 2017 Phase 2
NCT02578797 Aragon Pharmaceuticals, Inc. Castration-Resistant Prostate Cancer December 18, 2015 Phase 1
NCT02913196 Weill Medical College of Cornell University|Janssen Scientific Affairs, LLC Prostate Cancer Metastatic December 2016 Phase 1
NCT02924766 Janssen Research & Development, LLC Prostatic Neoplasms October 3, 2016 Phase 1
NCT02903368 Dana-Farber Cancer Institute|Janssen Scientific Affairs, LLC Prostate Cancer October 2016 Phase 2
NCT01946204 Aragon Pharmaceuticals, Inc. Prostatic Neoplasms October 2013 Phase 3
NCT02257736 Aragon Pharmaceuticals, Inc. Prostatic Neoplasms November 2014 Phase 3
NCT02531516 Aragon Pharmaceuticals, Inc. Prostatic Neoplasms November 19, 2015 Phase 3
NCT03141671 Dana-Farber Cancer Institute|Janssen Pharmaceutica Prostate Cancer June 2017 Phase 2
NCT02849990 University of Washington|Janssen Scientific Affairs, LLC|National Cancer Institute (NCI) Stage III Prostate Adenocarcinoma|Stage III Prostate Cancer|Stage IV Prostate Adenocarcinoma|Stage IV Prostate Cancer March 9, 2017 Phase 2
NCT03093272 Dana-Farber Cancer Institute|Janssen Pharmaceutica Prostate Cancer June 30, 2017 Phase 2
NCT02106507 Memorial Sloan Kettering Cancer Center|Aragon Pharmaceuticals, Inc. Prostate Cancer April 2014 Phase 1
NCT03009981 Alliance Foundation Trials, LLC.|Janssen Research & Development, LLC Prostate Cancer March 6, 2017 Phase 3
NCT02721979 University of Washington|Janssen Scientific Affairs, LLC|National Cancer Institute (NCI) Stage II Prostate Adenocarcinoma July 24, 2017 Phase 2
NCT01822041 Aragon Pharmaceuticals, Inc. Healthy March 2013 Phase 1
NCT02770391 Case Comprehensive Cancer Center Prostate Cancer October 2016 Phase 2
NCT01171898 Aragon Pharmaceuticals, Inc. Prostate Cancer July 26, 2010 Phase 1|Phase 2
NCT01792687 Aragon Pharmaceuticals, Inc. Prostate Cancer February 5, 2013 Phase 1
NCT03080116 Universitaire Ziekenhuizen Leuven Prostate Cancer|Neoadjuvant Therapy|Androgen Antagonists|Prostatectomy April 30, 2017 Phase 2
NCT01790126 Aragon Pharmaceuticals, Inc. Prostate Cancer March 4, 2013 Phase 2
NCT02949284 Rutgers, The State University of New Jersey|National Cancer Institute (NCI) Stage II Prostate Adenocarcinoma|Stage III Prostate Adenocarcinoma June 20, 2017 Phase 2
NCT02772588 Memorial Sloan Kettering Cancer Center|Janssen Pharmaceuticals|Weill Medical College of Cornell University|University of Michigan Prostate Cancer May 2016 Phase 2
NCT03098836 Daniel George, MD|Janssen Scientific Affairs, LLC|Duke University Prostate Cancer July 10, 2017 Phase 2
NCT03124433 Singapore General Hospital Cancer of the Prostate May 1, 2017 Phase 2
NCT02811809 Robert J Amato|Janssen Scientific Affairs, LLC|The University of Texas Health Science Center, Houston Prostate Cancer July 1, 2017 Phase 2
NCT03173859 University of Athens Prostatic Neoplasms, Castration-Resistant July 1, 2017 Phase 2
NCT02906605 Janssen Research & Development, LLC Prostatic Neoplasms, Castration-Resistant October 2016 Phase 2
NCT03088124 Institut Paoli-Calmettes|Janssen-Cilag Ltd. Low Risk Prostate Cancer April 28, 2017 Phase 2
NCT02489318 Aragon Pharmaceuticals, Inc. Prostate Cancer November 27, 2015 Phase 3
NCT02867020 Latin American Cooperative Oncology Group|Janssen Pharmaceuticals Prostate Cancer January 2017 Phase 2
NCT02789878 Instituto do Cancer do Estado de São Paulo|Janssen, LP Prostate Cancer June 2017 Phase 2
NCT02578797 Aragon Pharmaceuticals, Inc. Castration-Resistant Prostate Cancer December 18, 2015 Phase 1
NCT02913196 Weill Medical College of Cornell University|Janssen Scientific Affairs, LLC Prostate Cancer Metastatic December 2016 Phase 1
NCT02924766 Janssen Research & Development, LLC Prostatic Neoplasms October 3, 2016 Phase 1
NCT02903368 Dana-Farber Cancer Institute|Janssen Scientific Affairs, LLC Prostate Cancer October 2016 Phase 2
NCT01946204 Aragon Pharmaceuticals, Inc. Prostatic Neoplasms October 2013 Phase 3
NCT02257736 Aragon Pharmaceuticals, Inc. Prostatic Neoplasms November 2014 Phase 3
NCT02531516 Aragon Pharmaceuticals, Inc. Prostatic Neoplasms November 19, 2015 Phase 3
NCT03141671 Dana-Farber Cancer Institute|Janssen Pharmaceutica Prostate Cancer June 2017 Phase 2
NCT02849990 University of Washington|Janssen Scientific Affairs, LLC|National Cancer Institute (NCI) Stage III Prostate Adenocarcinoma|Stage III Prostate Cancer|Stage IV Prostate Adenocarcinoma|Stage IV Prostate Cancer March 9, 2017 Phase 2
NCT03093272 Dana-Farber Cancer Institute|Janssen Pharmaceutica Prostate Cancer June 30, 2017 Phase 2
NCT02106507 Memorial Sloan Kettering Cancer Center|Aragon Pharmaceuticals, Inc. Prostate Cancer April 2014 Phase 1
NCT03009981 Alliance Foundation Trials, LLC.|Janssen Research & Development, LLC Prostate Cancer March 6, 2017 Phase 3
NCT02721979 University of Washington|Janssen Scientific Affairs, LLC|National Cancer Institute (NCI) Stage II Prostate Adenocarcinoma July 24, 2017 Phase 2
NCT01822041 Aragon Pharmaceuticals, Inc. Healthy March 2013 Phase 1
NCT02770391 Case Comprehensive Cancer Center Prostate Cancer October 2016 Phase 2
NCT01171898 Aragon Pharmaceuticals, Inc. Prostate Cancer July 26, 2010 Phase 1|Phase 2
NCT01792687 Aragon Pharmaceuticals, Inc. Prostate Cancer February 5, 2013 Phase 1
NCT03080116 Universitaire Ziekenhuizen Leuven Prostate Cancer|Neoadjuvant Therapy|Androgen Antagonists|Prostatectomy April 30, 2017 Phase 2
NCT01790126 Aragon Pharmaceuticals, Inc. Prostate Cancer March 4, 2013 Phase 2
NCT02949284 Rutgers, The State University of New Jersey|National Cancer Institute (NCI) Stage II Prostate Adenocarcinoma|Stage III Prostate Adenocarcinoma June 20, 2017 Phase 2
NCT02772588 Memorial Sloan Kettering Cancer Center|Janssen Pharmaceuticals|Weill Medical College of Cornell University|University of Michigan Prostate Cancer May 2016 Phase 2
NCT03098836 Daniel George, MD|Janssen Scientific Affairs, LLC|Duke University Prostate Cancer July 10, 2017 Phase 2
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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]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
M.Wt

477.43

Formula

C₂₁H₁₅F₄N₅O₂S

CAS No.

956104-40-8

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥83.3 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 99.23%

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