Clinical data
  • X (Contraindicated)
Routes of
Pharmacokinetic data
Biological half-life 3–4 days[1]
CAS Number 956104-40-8
PubChem (CID) 24872560
ChemSpider 28424131
Chemical and physical data
Formula C21H15F4N5O2S
Molar mass 477.434713 g/mol
3D model (Jmol) Interactive image

Apalutamide (INN) (developmental code name ARN-509, also JNJ-56021927) is a non-steroidal antiandrogen that is under development for the treatment of prostate cancer.[2] It is similar to enzalutamide both structurally and pharmacologically,[3][4] acting as a selective competitive antagonist of the androgen receptor (AR), but shows some advantages, including greater potency and several-fold reduced central nervous system permeation.[2][5][6] Apalutamide is currently in phase III clinical trials for castration-resistant prostate cancer.[7]

Side effects

Apalutamide has been found to be well-tolerated in clinical trials thus far,[3][6] with the most common side effects reported including fatigue, nausea, abdominal pain, and diarrhea.[5][8][9]



Apalutamide is a silent antagonist of the AR and possesses 5- to 10-fold greater affinity for the AR than bicalutamide.[10][11]

Resistance in prostate cancer

Recently, the acquired F876L mutation of the AR identified in advanced prostate cancer cells was found to confer resistance to both enzalutamide and apalutamide.[12][13] A newer antiandrogen, darolutamide (ODM-201), is not affected by this mutation, nor has it been found to be affected by any other tested/well-known AR mutations.[14]

Apalutamide may be effective in a subset of prostate cancer patients with acquired resistance to abiraterone acetate.[3]

Other actions

Cytochrome P450 inducer

Apalutamide shows potent induction potential of CYP3A4 similarly to enzalutamide.[15][16]

GABAA receptor negative modulator

Apalutamide binds weakly to and inhibits the GABAA receptor in vitro similarly to enzalutamide (IC50 = 3.0 and 2.7 μM, respectively),[17] but due to its relatively lower central concentrations, may have a lower risk of seizures in comparison.[2][5][9]


The mean terminal half-life of apalutamide at steady-state is 3 to 4 days.[1]


The chemical structure of apalutamide is similar to that of enzalutamide.[10]

See also


  1. 1 2 Rathkopf, D. E.; Morris, M. J.; Fox, J. J.; Danila, D. C.; Slovin, S. F.; Hager, J. H.; Rix, P. J.; Chow Maneval, E.; Chen, I.; Gonen, M.; Fleisher, M.; Larson, S. M.; Sawyers, C. L.; Scher, H. I. (2013). "Phase I Study of ARN-509, a Novel Antiandrogen, in the Treatment of Castration-Resistant Prostate Cancer". Journal of Clinical Oncology. 31 (28): 3525–3530. doi:10.1200/JCO.2013.50.1684. ISSN 0732-183X.
  2. 1 2 3 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 (2012). "ARN-509: a novel antiandrogen for prostate cancer treatment". Cancer Res. 72 (6): 1494–503. doi:10.1158/0008-5472.CAN-11-3948. PMC 3306502Freely accessible. PMID 22266222.
  3. 1 2 3 Patel JC, Maughan BL, Agarwal AM, Batten JA, Zhang TY, Agarwal N (2013). "Emerging molecularly targeted therapies in castration refractory prostate cancer". Prostate Cancer. 2013: 981684. doi:10.1155/2013/981684. PMC 3684034Freely accessible. PMID 23819055.
  4. Ya-Xiong Tao (11 June 2014). Pharmacology and Therapeutics of Constitutively Active Receptors. Elsevier Science. pp. 351–. ISBN 978-0-12-417206-7. ARN-509 is related structurally to enzalutamide with greater in vivo activity in CRPC xenograft models (Clegg et al., 2012).
  5. 1 2 3 Schweizer MT, Antonarakis ES (2012). "Abiraterone and other novel androgen-directed strategies for the treatment of prostate cancer: a new era of hormonal therapies is born". Ther Adv Urol. 4 (4): 167–78. doi:10.1177/1756287212452196. PMC 3398601Freely accessible. PMID 22852027.
  6. 1 2 Rathkopf D, Scher HI (2013). "Androgen receptor antagonists in castration-resistant prostate cancer". Cancer J. 19 (1): 43–9. doi:10.1097/PPO.0b013e318282635a. PMC 3788593Freely accessible. PMID 23337756.
  7. Agarwal N, Di Lorenzo G, Sonpavde G, Bellmunt J (2014). "New agents for prostate cancer". Ann. Oncol. 25 (9): 1700–9. doi:10.1093/annonc/mdu038. PMID 24658665.
  8. Leibowitz-Amit R, Joshua AM (2012). "Targeting the androgen receptor in the management of castration-resistant prostate cancer: rationale, progress, and future directions". Curr Oncol. 19 (Suppl 3): S22–31. doi:10.3747/co.19.1281. PMC 3553559Freely accessible. PMID 23355790.
  9. 1 2 Pinto Á (2014). "Beyond abiraterone: new hormonal therapies for metastatic castration-resistant prostate cancer". Cancer Biol. Ther. 15 (2): 149–55. doi:10.4161/cbt.26724. PMC 3928129Freely accessible. PMID 24100689.
  10. 1 2 Kawahara, Takashi; Miyamoto, Hiroshi (2014). "Androgen Receptor Antagonists in the Treatment of Prostate Cancer". Clinical Immunology, Endocrine & Metabolic Drugs. 1 (1): 11–19. doi:10.2174/22127070114019990002. ISSN 2212-7070.
  11. Kim, Won; Ryan, Charles J. (2015). "Quo vadis: Advanced prostate cancer-clinical care and clinical research in the era of multiple androgen receptor-directed therapies". Cancer. 121 (3): 361–371. doi:10.1002/cncr.28929. ISSN 0008-543X.
  12. Joseph JD, Lu N, Qian J, Sensintaffar J, Shao G, Brigham D, Moon M, Maneval EC, Chen I, Darimont B, Hager JH (2013). "A clinically relevant androgen receptor mutation confers resistance to second-generation antiandrogens enzalutamide and ARN-509". Cancer Discov. 3 (9): 1020–9. doi:10.1158/2159-8290.CD-13-0226. PMID 23779130.
  13. Nelson WG, Yegnasubramanian S (2013). "Resistance emerges to second-generation antiandrogens in prostate cancer". Cancer Discov. 3 (9): 971–4. doi:10.1158/2159-8290.CD-13-0405. PMC 3800038Freely accessible. PMID 24019330.
  14. Moilanen AM, Riikonen R, Oksala R, Ravanti L, Aho E, Wohlfahrt G, Nykänen PS, Törmäkangas OP, Palvimo JJ, Kallio PJ (2015). "Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies". Sci Rep. 5: 12007. doi:10.1038/srep12007. PMC 4490394Freely accessible. PMID 26137992.
  15. Fizazi, Karim; Albiges, Laurence; Loriot, Yohann; Massard, Christophe (2015). "ODM-201: a new-generation androgen receptor inhibitor in castration-resistant prostate cancer". Expert Review of Anticancer Therapy. 15 (9): 1007–1017. doi:10.1586/14737140.2015.1081566. ISSN 1473-7140.
  16. Ivachtchenko, Alexandre V.; Mitkin, Oleg D.; Kudan, Elizaveta V.; Rjahovsky, Alexey A.; Vorobiev, Anton A.; Trifelenkov, Andrey S.; Shevkun, Natalia A.; Proskurina, Oxana V.; Kravchenko, Dmitry V.; Karapetian, Ruben N. (2014). "Preclinical Development of ONC1-13B, Novel Antiandrogen for Prostate Cancer Treatment". Journal of Cancer. 5 (2): 133–142. doi:10.7150/jca.7773. ISSN 1837-9664.
  17. Clegg, N. J.; Wongvipat, J.; Joseph, J. D.; Tran, C.; Ouk, S.; Dilhas, A.; Chen, Y.; Grillot, K.; Bischoff, E. D.; Cai, L.; Aparicio, A.; Dorow, S.; Arora, V.; Shao, G.; Qian, J.; Zhao, H.; Yang, G.; Cao, C.; Sensintaffar, J.; Wasielewska, T.; Herbert, M. R.; Bonnefous, C.; Darimont, B.; Scher, H. I.; Smith-Jones, P.; Klang, M.; Smith, N. D.; De Stanchina, E.; Wu, N.; Ouerfelli, O.; Rix, P. J.; Heyman, R. A.; Jung, M. E.; Sawyers, C. L.; Hager, J. H. (2012). "ARN-509: A Novel Antiandrogen for Prostate Cancer Treatment". Cancer Research. 72 (6): 1494–1503. doi:10.1158/0008-5472.CAN-11-3948. ISSN 0008-5472.

External links

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