Daprodustat

Daprodustat (INN, trade name Duvroq in Japan, development code GSK1278863) is a drug which acts as a HIF prolyl-hydroxylase inhibitor and thereby increases endogenous production of erythropoietin, which stimulates production of hemoglobin and red blood cells. It is in Phase III clinical trials for the treatment of anemia caused by chronic kidney disease.[1][2][3]

Daprodustat
Clinical data
Other namesGSK1278863
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Identifiers
IUPAC name
  • 2-[(1,3-dicyclohexyl-2,4,6-trioxo-1,3-diazinane-5-carbonyl)amino]acetic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
ECHA InfoCard100.219.426
Chemical and physical data
FormulaC19H27N3O6
Molar mass393.440 g·mol−1
3D model (JSmol)
SMILES
  • C3CCCCC3n(c(=O)c1C(=O)NCC(=O)O)c(=O)n(c1O)C2CCCCC2
InChI
  • InChI=1S/C19H27N3O6/c23-14(24)11-20-16(25)15-17(26)21(12-7-3-1-4-8-12)19(28)22(18(15)27)13-9-5-2-6-10-13/h12-13,26H,1-11H2,(H,20,25)(H,23,24)
  • Key:NVTKJBXOBFRPLQ-UHFFFAOYSA-N

Daprodustat was approved in Japan in June 2020 for the treatment of patients with anemia due to chronic kidney disease.[4]

Due to its potential applications in athletic doping, it has also been incorporated into screens for performance-enhancing drugs.[5]

In October 2022, US Food and Drug Administration (FDA) Cardiovascular and Renal Drugs Advisory Committee (CRDAC) recommended daprodustat for adult dialysis patients with anaemia of chronic kidney disease (CKD). The advisory committee experts, however, voted against the use of daprodustat in non-dialysis patients with anaemia of CKD, citing increased safety risks such as heart failure and bleeding gastric erosions.[6]

See also

References
  1. Schmid H, Jelkmann W (August 2016). "Investigational therapies for renal disease-induced anemia". Expert Opinion on Investigational Drugs. 25 (8): 901–16. doi:10.1080/13543784.2016.1182981. PMID 27122198. S2CID 32493057.
  2. Ariazi JL, Duffy KJ, Adams DF, Fitch DM, Luo L, Pappalardi M, et al. (December 2017). "Discovery and Preclinical Characterization of GSK1278863 (Daprodustat), a Small Molecule Hypoxia Inducible Factor-Prolyl Hydroxylase Inhibitor for Anemia". The Journal of Pharmacology and Experimental Therapeutics. 363 (3): 336–347. doi:10.1124/jpet.117.242503. PMID 28928122.
  3. Singh, Ajay K.; Carroll, Kevin; McMurray, John J.V.; Solomon, Scott; Jha, Vivekanand; Johansen, Kirsten L.; Lopes, Renato D.; Macdougall, Iain C.; Obrador, Gregorio T.; Waikar, Sushrut S.; Wanner, Christoph; Wheeler, David C.; Więcek, Andrzej; Blackorby, Allison; Cizman, Borut (2021-12-16). "Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis". New England Journal of Medicine. 385 (25): 2313–2324. doi:10.1056/NEJMoa2113380. ISSN 0028-4793. PMID 34739196.
  4. "GSK receives first regulatory approval for Duvroq (daprodustat) in Japan for patients with anaemia due to chronic kidney disease" (Press release). GSK. 29 June 2020.
  5. Thevis M, Milosovich S, Licea-Perez H, Knecht D, Cavalier T, Schänzer W (August 2016). "Mass spectrometric characterization of a prolyl hydroxylase inhibitor GSK1278863, its bishydroxylated metabolite, and its implementation into routine doping controls". Drug Testing and Analysis. 8 (8): 858–63. doi:10.1002/dta.1870. PMID 26361079.
  6. "UPDATED CONTACT INFORMATION: October 26, 2022 Meeting of the Cardiovascular and Renal Drugs Advisory Committee Meeting Announcement - 10/26/2022". FDA. 2022-10-26. Retrieved 2022-10-31.


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