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MedKoo Cat#: 204420 | Name: Apalutamide (ARN-509)
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Apalutamide, also known as ARN-509 and JNJ-56021927 , is an androgen receptor antagonist with potential antineoplastic activity. ARN-509 binds to AR in target tissues thereby preventing androgen-induced receptor activation and facilitating the formation of inactive complexes that cannot be translocated to the nucleus. This prevents binding to and transcription of AR-responsive genes. This ultimately inhibits the expression of genes that regulate prostate cancer cell proliferation and may lead to an inhibition of cell growth in AR-expressing tumor cells.

Chemical Structure

Apalutamide (ARN-509)
Apalutamide (ARN-509)
CAS#956104-40-8 (free base)

Theoretical Analysis

MedKoo Cat#: 204420

Name: Apalutamide (ARN-509)

CAS#: 956104-40-8 (free base)

Chemical Formula: C21H15F4N5O2S

Exact Mass: 477.0883

Molecular Weight: 477.43

Elemental Analysis: C, 52.83; H, 3.17; F, 15.92; N, 14.67; O, 6.70; S, 6.72

Price and Availability

Size Price Availability Quantity
10mg USD 110.00 Ready to ship
25mg USD 220.00 Ready to ship
50mg USD 380.00 Ready to ship
100mg USD 650.00 Ready to ship
200mg USD 1,050.00 Ready to ship
500mg USD 2,250.00 Ready to ship
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Related CAS #
1505451-73-9 (ethanol) 956104-40-8 (free base) 1505451-74-0 (hydrate) 1505451-77-3 (DMSO) 2376466-25-8 (acetate)
Synonym
ARN509; ARN 509; ARN-509; JNJ56021927; JNJ-56021927; JNJ 56021927; Apalutamide
IUPAC/Chemical Name
4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-fluoro-N-methylbenzamide
InChi Key
HJBWBFZLDZWPHF-UHFFFAOYSA-N
InChi Code
InChI=1S/C21H15F4N5O2S/c1-27-17(31)13-4-3-11(8-15(13)22)30-19(33)29(18(32)20(30)5-2-6-20)12-7-14(21(23,24)25)16(9-26)28-10-12/h3-4,7-8,10H,2,5-6H2,1H3,(H,27,31)
SMILES Code
O=C(NC)C1=CC=C(N(C(N(C2=CC(C(F)(F)F)=C(C#N)N=C2)C3=O)=S)C43CCC4)C=C1F
Appearance
white to off-white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO (50 mg/mL)
Shelf Life
>5 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
The chemical structure of ARN-509 is very similar structure to  that of Enzalutamide (MDV3100) with two minor modifications: (a) two methyl groups in the 5-member ring of MDV3100 is linked by a CH2 group in ARN-509; (b) the carbon atom in the benzene ring of MDV3100 is replaced by a nitrogen atom in ARN-509. ARN-509 is considered as a Me-Too drug of Enzalutamide (MDV3100). ARN-509 was claimed to be more active than Enzalutamide (MDV3100).    ARN-509 is a novel 2nd Generation anti-androgen that is targeted to treat castration resistant prostate cancers where 1st generation anti-androgens fail.  ARN-509 is unique in its action in that it inhibits both AR nuclear translocation and AR binding to androgen response elements in DNA. Importantly, and in contrast to the first-generation anti-androgen bicalutamide, it exhibits no agonist activity in prostate cancer cells that over-express AR. ARN-509 is easily synthesized, and its oral bioavailability and long half-life allow for once-daily oral dosing. In addition, its excellent preclinical safety profile makes it well suited as either a mono- or a combination therapy across the entire spectrum of prostate cancer disease states. (source: http://www.aragonpharm.com/programs/arn509.htm).    ARN-509 is  a competitive AR inhibitor, which is fully antagonistic to AR overexpression, a common and important feature of CRPC. ARN-509 was optimized for inhibition of AR transcriptional activity and prostate cancer cell proliferation, pharmacokinetics and in vivo efficacy. In contrast to bicalutamide, ARN-509 lacked significant agonist activity in preclinical models of CRPC. Moreover, ARN-509 lacked inducing activity for AR nuclear localization or DNA binding. In a clinically valid murine xenograft model of human CRPC, ARN-509 showed greater efficacy than MDV3100. Maximal therapeutic response in this model was achieved at 30 mg/kg/day of ARN-509 , whereas the same response required 100 mg/kg/day of MDV3100 and higher steady-state plasma concentrations. Thus, ARN-509 exhibits characteristics predicting a higher therapeutic index with a greater potential to reach maximally efficacious doses in man than current AR antagonists. Our findings offer preclinical proof of principle for ARN-509 as a promising therapeutic in both castration-sensitive and castration-resistant forms of prostate cancer. (source: Cancer Res. 2012 Jan 20. [Epub ahead of print] ) (source: Cancer Res. 2012 Jan 20. [Epub ahead of print] )    
Biological target:
Apalutamide (ARN-509) is a selective and competitive androgen receptor inhibitor with IC50 of 16 nM in a cell-free assay, useful for prostate cancer treatment.
In vitro activity:
ARN-509 (< 10 μM) inhibits androgen-mediated induction or repression of mRNA expression levels for 13 endogenous genes including PSA and TMPRSS2 in the LNCaP/AR prostate cancer cell line. ARN-509 (< 10 μM) inhibits the proliferative effect of R1881 (30 pM) in the LNCaP/AR prostate cancer cell line. ARN-509 (10 μM) impairs AR nuclear localization and thus reduces the concentration of AR available to bind androgen response elements (ARE) in LNCaP cells expressing AR-EYFP. ARN-509 (10 μM) is able to effectively compete with R1881 (1 nM) and prevent AR from binding to promoter regions. ARN-509 inhibits R1881-induced VP16-AR–mediated transcription with IC50 of 0.2 μM in Hep-G2 cells expressing a VP16-AR fusion protein and an ARE-driven luciferase reporter. Reference: Cancer Res. 2012 Mar 15;72(6):1494-503. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22266222/
In vivo activity:
ARN-509 (10 mg/kg/d, oral) inhibits tumor growth with decreased proliferative index and increased apoptotic rate in castrate male immunodeficient mice harboring LNCaP/AR-luc xenograft tumors. ARN-509 dose dependently inhibits tumor growth with highest efficacy at dose of 30 mg/kg/day in castrate male immunodeficient mice harboring LNCaP/AR-luc xenograft tumors. ARN-509 dosed at 10 mg/kg/d for 28 days results in a 3-fold reduction in prostates weight associated with lacking glandular secretory activity and 1.7-fold reduction in epididymis weight in adult male dogs. ARN-509 (10 mg/kg/d, oral) inhibits cell proliferation of prostate tissues in adult male dogs. Reference: Cancer Res. 2012 Mar 15;72(6):1494-503. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22266222/
Solvent mg/mL mM
Solubility
DMSO 50.0 104.73
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 477.43 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Clegg NJ, Wongvipat J, Joseph JD, Tran C, Ouk S, Dilhas A, Chen Y, Grillot K, Bischoff ED, Cai L, Aparicio A, Dorow S, Arora V, Shao G, Qian J, Zhao H, Yang G, Cao C, Sensintaffar J, Wasielewska T, Herbert MR, Bonnefous C, Darimont B, Scher HI, Smith-Jones P, Klang M, Smith ND, De Stanchina E, Wu N, Ouerfelli O, Rix PJ, Heyman RA, Jung ME, Sawyers CL, Hager JH. ARN-509: a novel antiandrogen for prostate cancer treatment. Cancer Res. 2012 Mar 15;72(6):1494-503. doi: 10.1158/0008-5472.CAN-11-3948. Epub 2012 Jan 20. PMID: 22266222; PMCID: PMC3306502. 2. Sun J, Wang D, Guo L, Fang S, Wang Y, Xing R. Androgen Receptor Regulates the Growth of Neuroblastoma Cells in vitro and in vivo. Front Neurosci. 2017 Mar 7;11:116. doi: 10.3389/fnins.2017.00116. PMID: 28326012; PMCID: PMC5339338.
In vitro protocol:
1. Clegg NJ, Wongvipat J, Joseph JD, Tran C, Ouk S, Dilhas A, Chen Y, Grillot K, Bischoff ED, Cai L, Aparicio A, Dorow S, Arora V, Shao G, Qian J, Zhao H, Yang G, Cao C, Sensintaffar J, Wasielewska T, Herbert MR, Bonnefous C, Darimont B, Scher HI, Smith-Jones P, Klang M, Smith ND, De Stanchina E, Wu N, Ouerfelli O, Rix PJ, Heyman RA, Jung ME, Sawyers CL, Hager JH. ARN-509: a novel antiandrogen for prostate cancer treatment. Cancer Res. 2012 Mar 15;72(6):1494-503. doi: 10.1158/0008-5472.CAN-11-3948. Epub 2012 Jan 20. PMID: 22266222; PMCID: PMC3306502. 2. Sun J, Wang D, Guo L, Fang S, Wang Y, Xing R. Androgen Receptor Regulates the Growth of Neuroblastoma Cells in vitro and in vivo. Front Neurosci. 2017 Mar 7;11:116. doi: 10.3389/fnins.2017.00116. PMID: 28326012; PMCID: PMC5339338.
In vivo protocol:
1. Clegg NJ, Wongvipat J, Joseph JD, Tran C, Ouk S, Dilhas A, Chen Y, Grillot K, Bischoff ED, Cai L, Aparicio A, Dorow S, Arora V, Shao G, Qian J, Zhao H, Yang G, Cao C, Sensintaffar J, Wasielewska T, Herbert MR, Bonnefous C, Darimont B, Scher HI, Smith-Jones P, Klang M, Smith ND, De Stanchina E, Wu N, Ouerfelli O, Rix PJ, Heyman RA, Jung ME, Sawyers CL, Hager JH. ARN-509: a novel antiandrogen for prostate cancer treatment. Cancer Res. 2012 Mar 15;72(6):1494-503. doi: 10.1158/0008-5472.CAN-11-3948. Epub 2012 Jan 20. PMID: 22266222; PMCID: PMC3306502. 2. Sun J, Wang D, Guo L, Fang S, Wang Y, Xing R. Androgen Receptor Regulates the Growth of Neuroblastoma Cells in vitro and in vivo. Front Neurosci. 2017 Mar 7;11:116. doi: 10.3389/fnins.2017.00116. PMID: 28326012; PMCID: PMC5339338.
1: Clegg NJ, Wongvipat J, Joseph JD, Tran C, Ouk S, Dilhas A, Chen Y, Grillot K, Bischoff ED, Cai L, Aparicio A, Dorow S, Arora V, Shao G, Qian J, Zhao H, Yang G, Cao C, Sensintaffar J, Wasielewska T, Herbert MR, Bonnefous C, Darimont B, Scher HI, Smith-Jones P, Klang M, Smith ND, De Stanchina E, Wu N, Ouerfelli O, Rix PJ, Heyman RA, Jung ME, Sawyers CL, Hager JH. ARN-509: a novel antiandrogen for prostate cancer treatment. Cancer Res. 2012 Mar 15;72(6):1494-503. doi: 10.1158/0008-5472.CAN-11-3948. Epub 2012 Jan 20. PMID: 22266222; PMCID: PMC3306502. 2: Chi KN, Agarwal N, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juárez Soto Á, Merseburger AS, Özgüroğlu M, Uemura H, Ye D, Deprince K, Naini V, Li J, Cheng S, Yu MK, Zhang K, Larsen JS, McCarthy S, Chowdhury S; TITAN Investigators. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2019 Jul 4;381(1):13-24. doi: 10.1056/NEJMoa1903307. Epub 2019 May 31. PMID: 31150574. 3: Desai K, McManus JM, Sharifi N. Hormonal Therapy for Prostate Cancer. Endocr Rev. 2021 May 25;42(3):354-373. doi: 10.1210/endrev/bnab002. PMID: 33480983; PMCID: PMC8152444. 4: Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, De Porre P, Smith AA, Brookman-May SD, Li S, Zhang K, Rooney B, Lopez-Gitlitz A, Small EJ. Apalutamide and Overall Survival in Prostate Cancer. Eur Urol. 2021 Jan;79(1):150-158. doi: 10.1016/j.eururo.2020.08.011. Epub 2020 Sep 6. PMID: 32907777. 5: Chi KN, Chowdhury S, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juárez A, Merseburger AS, Özgüroğlu M, Uemura H, Ye D, Brookman-May S, Mundle SD, McCarthy SA, Larsen JS, Sun W, Bevans KB, Zhang K, Bandyopadhyay N, Agarwal N. Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study. J Clin Oncol. 2021 Jul 10;39(20):2294-2303. doi: 10.1200/JCO.20.03488. Epub 2021 Apr 29. PMID: 33914595. 6: Swami U, McFarland TR, Nussenzveig R, Agarwal N. Advanced Prostate Cancer: Treatment Advances and Future Directions. Trends Cancer. 2020 Aug;6(8):702-715. doi: 10.1016/j.trecan.2020.04.010. Epub 2020 Jun 10. PMID: 32534790. 7: Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, Lopez-Gitlitz A, Trudel GC, Espina BM, Shu Y, Park YC, Rackoff WR, Yu MK, Small EJ; SPARTAN Investigators. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med. 2018 Apr 12;378(15):1408-1418. doi: 10.1056/NEJMoa1715546. Epub 2018 Feb 8. PMID: 29420164. 8: He Y, Xu W, Xiao YT, Huang H, Gu D, Ren S. Targeting signaling pathways in prostate cancer: mechanisms and clinical trials. Signal Transduct Target Ther. 2022 Jun 24;7(1):198. doi: 10.1038/s41392-022-01042-7. PMID: 35750683; PMCID: PMC9232569. 9: Ritch C, Cookson M. Recent trends in the management of advanced prostate cancer. F1000Res. 2018 Sep 21;7:F1000 Faculty Rev-1513. doi: 10.12688/f1000research.15382.1. PMID: 30345007; PMCID: PMC6173112. 10: Mori K, Mostafaei H, Sari Motlagh R, Pradere B, Quhal F, Laukhtina E, Schuettfort VM, Kramer G, Abufaraj M, Karakiewicz PI, Kimura T, Egawa S, Shariat SF. Systemic therapies for metastatic hormone-sensitive prostate cancer: network meta-analysis. BJU Int. 2022 Apr;129(4):423-433. doi: 10.1111/bju.15507. Epub 2021 Jul 21. PMID: 34171173; PMCID: PMC9291853. 11: Menges D, Yebyo HG, Sivec-Muniz S, Haile SR, Barbier MC, Tomonaga Y, Schwenkglenks M, Puhan MA. Treatments for Metastatic Hormone-sensitive Prostate Cancer: Systematic Review, Network Meta-analysis, and Benefit-harm assessment. Eur Urol Oncol. 2022 Dec;5(6):605-616. doi: 10.1016/j.euo.2022.04.007. Epub 2022 May 20. PMID: 35599144. 12: Kato M. Editorial Comments to Patient-reported outcomes of a phase II neoadjuvant Apalutamide (ARN-509) and radical prostatectomy in treatment of intermediate- to high-risk prostate cancer (NEAR) trial. Int J Urol. 2022 Nov;29(11):1330. doi: 10.1111/iju.15013. Epub 2022 Aug 24. PMID: 36001637. 13: Wang L, Paller CJ, Hong H, De Felice A, Alexander GC, Brawley O. Comparison of Systemic Treatments for Metastatic Castration-Sensitive Prostate Cancer: A Systematic Review and Network Meta-analysis. JAMA Oncol. 2021 Mar 1;7(3):412-420. doi: 10.1001/jamaoncol.2020.6973. PMID: 33443584; PMCID: PMC7809610. 14: Wenzel M, Nocera L, Collà Ruvolo C, Würnschimmel C, Tian Z, Shariat SF, Saad F, Tilki D, Graefen M, Kluth LA, Briganti A, Mandel P, Montorsi F, Chun FKH, Karakiewicz PI. Overall survival and adverse events after treatment with darolutamide vs. apalutamide vs. enzalutamide for high-risk non-metastatic castration-resistant prostate cancer: a systematic review and network meta- analysis. Prostate Cancer Prostatic Dis. 2022 Feb;25(2):139-148. doi: 10.1038/s41391-021-00395-4. Epub 2021 May 30. Erratum in: Prostate Cancer Prostatic Dis. 2023 Mar 10;: PMID: 34054128; PMCID: PMC9184262. 15: Ganesh K, Wu C, O'Rourke KP, Szeglin BC, Zheng Y, Sauvé CG, Adileh M, Wasserman I, Marco MR, Kim AS, Shady M, Sanchez-Vega F, Karthaus WR, Won HH, Choi SH, Pelossof R, Barlas A, Ntiamoah P, Pappou E, Elghouayel A, Strong JS, Chen CT, Harris JW, Weiser MR, Nash GM, Guillem JG, Wei IH, Kolesnick RN, Veeraraghavan H, Ortiz EJ, Petkovska I, Cercek A, Manova-Todorova KO, Saltz LB, Lavery JA, DeMatteo RP, Massagué J, Paty PB, Yaeger R, Chen X, Patil S, Clevers H, Berger MF, Lowe SW, Shia J, Romesser PB, Dow LE, Garcia-Aguilar J, Sawyers CL, Smith JJ. A rectal cancer organoid platform to study individual responses to chemoradiation. Nat Med. 2019 Oct;25(10):1607-1614. doi: 10.1038/s41591-019-0584-2. Epub 2019 Oct 7. PMID: 31591597; PMCID: PMC7385919. 16: Cattrini C, Caffo O, De Giorgi U, Mennitto A, Gennari A, Olmos D, Castro E. Apalutamide, Darolutamide and Enzalutamide for Nonmetastatic Castration- Resistant Prostate Cancer (nmCRPC): A Critical Review. Cancers (Basel). 2022 Mar 31;14(7):1792. doi: 10.3390/cancers14071792. PMID: 35406564; PMCID: PMC8997634. 17: Jacob A, Raj R, Allison DB, Myint ZW. Androgen Receptor Signaling in Prostate Cancer and Therapeutic Strategies. Cancers (Basel). 2021 Oct 28;13(21):5417. doi: 10.3390/cancers13215417. PMID: 34771580; PMCID: PMC8582395. 18: Small EJ, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, De Porre P, Smith AA, Zhang K, Lopez-Gitlitz A, Smith MR. Apalutamide and overall survival in non-metastatic castration- resistant prostate cancer. Ann Oncol. 2019 Nov 1;30(11):1813-1820. doi: 10.1093/annonc/mdz397. PMID: 31560066; PMCID: PMC6927320. 19: Cattrini C, España R, Mennitto A, Bersanelli M, Castro E, Olmos D, Lorente D, Gennari A. Optimal Sequencing and Predictive Biomarkers in Patients with Advanced Prostate Cancer. Cancers (Basel). 2021 Sep 8;13(18):4522. doi: 10.3390/cancers13184522. PMID: 34572748; PMCID: PMC8467385. 20: Nevedomskaya E, Baumgart SJ, Haendler B. Recent Advances in Prostate Cancer Treatment and Drug Discovery. Int J Mol Sci. 2018 May 4;19(5):1359. doi: 10.3390/ijms19051359. PMID: 29734647; PMCID: PMC5983695.