Darolutamide

Darolutamide
Clinical data
Trade namesNubeqa
Other namesDarramamide, ODM-201, BAY-1841788
AHFS/Drugs.comMonograph
MedlinePlusa619045
License data
Pregnancy
category
  • AU: X (High risk)
Routes of
administration		By mouth
Drug classNonsteroidal antiandrogen
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability≤30%[4]
Protein bindingDarolutamide: 92%[4]
Ketodarolutamide: 99.8%[4]
MetabolismDehydrogenation (CYP3A4), glucuronidation (UGT1A9, UGT1A1)[4]
MetabolitesKetodarolutamide[4][7]
Elimination half-life16–20 hours[4][7]
ExcretionUrine: 63.4%[4]
Feces: 32.4%[4]
Identifiers
  • N-((S)-1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.264.885 Edit this at Wikidata
Chemical and physical data
FormulaC19H19ClN6O2
Molar mass398.85 g·mol−1
3D model (JSmol)
  • C[C@@H](Cn1ccc(n1)c2ccc(c(c2)Cl)C#N)NC(=O)c3cc([nH]n3)C(C)O
  • InChI=1S/C19H19ClN6O2/c1-11(22-19(28)18-8-17(12(2)27)23-24-18)10-26-6-5-16(25-26)13-3-4-14(9-21)15(20)7-13/h3-8,11-12,27H,10H2,1-2H3,(H,22,28)(H,23,24)/t11-,12?/m0/s1
  • Key:BLIJXOOIHRSQRB-PXYINDEMSA-N
  (verify)

Darolutamide, sold under the brand name Nubeqa, is an antiandrogen medication which is used in the treatment of non-metastatic castration-resistant prostate cancer in men.[8][4][5][9][10] It is specifically approved to treat non-metastatic castration-resistant prostate cancer (nmCRPC) in conjunction with surgical or medical castration.[4] The medication is taken by mouth twice per day with food.[4]

Side effects of darolutamide added to castration may include fatigue, asthenia, pain in the arms and legs, and rash.[4] Darolutamide is a nonsteroidal antiandrogen (NSAA), and acts as a selective antagonist of the androgen receptor (AR).[4][9][10] It has been referred to as a second- or third-generation NSAA.[11][12]

Darolutamide was patented in 2011 [13] and was approved for medical use in USA in July 2019,[8][14] in the European Union in March 2020 [5] in Australia in July 2020.[15] and in Canada in 2020,

  1. ^ "Nubeqa Australian prescription medicine decision summary". Therapeutic Goods Administration (TGA). 4 March 2020. Retrieved 16 August 2020.
  2. ^ "Product Monograph" (PDF). hres.ca. Retrieved 25 October 2023.
  3. ^ "Summary Basis of Decision (SBD) for Nubeqa". Health Canada. 23 October 2014. Retrieved 29 May 2022.
  4. ^ a b c d e f g h i j k l m n "Nubeqa- darolutamide tablet, film coated". DailyMed. 31 July 2019. Retrieved 22 November 2019.
  5. ^ a b c "Nubeqa EPAR". European Medicines Agency (EMA). 29 January 2020. Retrieved 16 August 2020.
  6. ^ "Nubeqa Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  7. ^ a b Fizazi K, Massard C, Bono P, Jones R, Kataja V, James N, et al. (August 2014). "Activity and safety of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (ARADES): an open-label phase 1 dose-escalation and randomised phase 2 dose expansion trial" (PDF). The Lancet. Oncology. 15 (9): 975–85. doi:10.1016/S1470-2045(14)70240-2. PMID 24974051.
  8. ^ a b Public Domain This article incorporates text from this source, which is in the public domain: "FDA approves darolutamide for non-metastatic castration-resistant prostate cancer". U.S. Food and Drug Administration (FDA) (Press release). 31 July 2019. Archived from the original on 23 November 2019. Retrieved 22 November 2019.
  9. ^ a b Fizazi K, Albiges L, Loriot Y, Massard C (2015). "ODM-201: a new-generation androgen receptor inhibitor in castration-resistant prostate cancer". Expert Review of Anticancer Therapy. 15 (9): 1007–17. doi:10.1586/14737140.2015.1081566. PMC 4673554. PMID 26313416.
  10. ^ a b Moilanen AM, Riikonen R, Oksala R, Ravanti L, Aho E, Wohlfahrt G, et al. (July 2015). "Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies". Scientific Reports. 5: 12007. Bibcode:2015NatSR...512007M. doi:10.1038/srep12007. PMC 4490394. PMID 26137992.
  11. ^ Shore ND (June 2017). "Darolutamide (ODM-201) for the treatment of prostate cancer". Expert Opinion on Pharmacotherapy. 18 (9): 945–952. doi:10.1080/14656566.2017.1329820. PMID 28490267. S2CID 20624649.
  12. ^ Crawford ED, Schellhammer PF, McLeod DG, Moul JW, Higano CS, Shore N, et al. (November 2018). "Androgen Receptor Targeted Treatments of Prostate Cancer: 35 Years of Progress with Antiandrogens". The Journal of Urology. 200 (5): 956–966. doi:10.1016/j.juro.2018.04.083. PMID 29730201. S2CID 19162538.
  13. ^ Cite error: The named reference WO2011051540A1 was invoked but never defined (see the help page).
  14. ^ Public Domain This article incorporates text from this source, which is in the public domain: "Drug Trials Snapshots: Nubeqa". U.S. Food and Drug Administration (FDA). 9 August 2019. Archived from the original on 23 November 2019. Retrieved 22 November 2019.
  15. ^ "AusPAR: Darolutamide". Therapeutic Goods Administration (TGA). 3 August 2020. Retrieved 22 September 2020.