WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206434
CAS#: 960539-70-2
Description: Daprodustat, also known as GSK1278863, is a novel HIF-prolyl hydroxylase inhibitor. Hypoxia inducible factor (HIF) stabilization by HIF-prolyl hydroxylase (PHD) inhibitors may improve ischemic conditions such as peripheral artery disease (PAD). Short-term treatment with a novel HIF-prolyl hydroxylase inhibitor (GSK1278863) failed to improve measures of performance in subjects with claudication-limited peripheral artery disease.
MedKoo Cat#: 206434
Name: Daprodustat
CAS#: 960539-70-2
Chemical Formula: C19H27N3O6
Exact Mass: 393.18999
Molecular Weight: 393.44
Elemental Analysis: C, 58.00; H, 6.92; N, 10.68; O, 24.40
Synonym: GSK1278863; GSK 1278863; GSK-1278863; Daprodustat
IUPAC/Chemical Name: (1,3-dicyclohexyl-2,4,6-trioxohexahydropyrimidine-5-carbonyl)glycine
InChi Key: RUEYEZADQJCKGV-UHFFFAOYSA-N
InChi Code: 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/h12-13,15H,1-11H2,(H,20,25)(H,23,24)
SMILES Code: O=C(O)CNC(C(C(N1C2CCCCC2)=O)C(N(C3CCCCC3)C1=O)=O)=O
Appearance: 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 (3mg/mL), not in water
Shelf Life: >2 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
The following data is based on the product molecular weight 393.44 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.
| 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 |
1: Xie D, Wang J, Wu X, Li M. Effect of daprodustat on anemia in patients with chronic kidney disease: a meta-analysis. Int Urol Nephrol. 2018 Dec;50(12):2201-2206. doi: 10.1007/s11255-018-1940-8. Epub 2018 Aug 2. Review. PubMed PMID: 30073615.
2: Cizman B, Sykes AP, Paul G, Zeig S, Cobitz AR. An Exploratory Study of Daprodustat in Erythropoietin-Hyporesponsive Subjects. Kidney Int Rep. 2018 Mar 3;3(4):841-850. doi: 10.1016/j.ekir.2018.02.009. eCollection 2018 Jul. PubMed PMID: 29989040; PubMed Central PMCID: PMC6035126.
3: Caltabiano S, Mahar KM, Lister K, Tenero D, Ravindranath R, Cizman B, Cobitz AR. The drug interaction potential of daprodustat when coadministered with pioglitazone, rosuvastatin, or trimethoprim in healthy subjects. Pharmacol Res Perspect. 2018 Mar 9;6(2):e00327. doi: 10.1002/prp2.327. eCollection 2018 Apr. PubMed PMID: 29545948; PubMed Central PMCID: PMC5843756.
4: Ariazi JL, Duffy KJ, Adams DF, Fitch DM, Luo L, Pappalardi M, Biju M, DiFilippo EH, Shaw T, Wiggall K, Erickson-Miller C. Discovery and Preclinical Characterization of GSK1278863 (Daprodustat), a Small Molecule Hypoxia Inducible Factor-Prolyl Hydroxylase Inhibitor for Anemia. J Pharmacol Exp Ther. 2017 Dec;363(3):336-347. doi: 10.1124/jpet.117.242503. Epub 2017 Sep 19. PubMed PMID: 28928122.
5: Haase VH. HIF-prolyl hydroxylases as therapeutic targets in erythropoiesis and iron metabolism. Hemodial Int. 2017 Jun;21 Suppl 1:S110-S124. doi: 10.1111/hdi.12567. Review. PubMed PMID: 28449418; PubMed Central PMCID: PMC5526677.
6: Caltabiano S, Collins J, Serbest G, Morgan L, Smith DA, Ravindranath R, Cobitz AR. A Randomized, Placebo- and Positive-Controlled, Single-Dose, Crossover Thorough QT/QTc Study Assessing the Effect of Daprodustat on Cardiac Repolarization in Healthy Subjects. Clin Pharmacol Drug Dev. 2017 Nov;6(6):627-640. doi: 10.1002/cpdd.342. Epub 2017 Apr 17. PubMed PMID: 28419747.
7: Gupta N, Wish JB. Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors: A Potential New Treatment for Anemia in Patients With CKD. Am J Kidney Dis. 2017 Jun;69(6):815-826. doi: 10.1053/j.ajkd.2016.12.011. Epub 2017 Feb 24. Review. Erratum in: Am J Kidney Dis. 2017 Jun;69(6):869. PubMed PMID: 28242135.
8: Locatelli F, Fishbane S, Block GA, Macdougall IC. Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients. Am J Nephrol. 2017;45(3):187-199. doi: 10.1159/000455166. Epub 2017 Jan 25. Review. PubMed PMID: 28118622.
9: Akizawa T, Tsubakihara Y, Nangaku M, Endo Y, Nakajima H, Kohno T, Imai Y, Kawase N, Hara K, Lepore J, Cobitz A. Effects of Daprodustat, a Novel Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor on Anemia Management in Japanese Hemodialysis Subjects. Am J Nephrol. 2017;45(2):127-135. doi: 10.1159/000454818. Epub 2016 Dec 16. PubMed PMID: 27978511.
10: Brigandi RA, Johnson B, Oei C, Westerman M, Olbina G, de Zoysa J, Roger SD, Sahay M, Cross N, McMahon L, Guptha V, Smolyarchuk EA, Singh N, Russ SF, Kumar S; PHI112844 Investigators. A Novel Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor (GSK1278863) for Anemia in CKD: A 28-Day, Phase 2A Randomized Trial. Am J Kidney Dis. 2016 Jun;67(6):861-71. doi: 10.1053/j.ajkd.2015.11.021. Epub 2016 Jan 27. PubMed PMID: 26827289.
11: Licea Perez H, Knecht D, Evans CA. Overcoming bioanalytical challenges associated with the separation and quantitation of GSK1278863, a HIF-prolyl hydroxylase inhibitor, and its 14 stereoisomeric metabolites. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Jan 15;1009-1010:7-16. doi: 10.1016/j.jchromb.2015.11.057. Epub 2015 Dec 4. PubMed PMID: 26688343.
12: Hara K, Takahashi N, Wakamatsu A, Caltabiano S. Pharmacokinetics, pharmacodynamics and safety of single, oral doses of GSK1278863, a novel HIF-prolyl hydroxylase inhibitor, in healthy Japanese and Caucasian subjects. Drug Metab Pharmacokinet. 2015 Dec;30(6):410-8. doi: 10.1016/j.dmpk.2015.08.004. Epub 2015 Aug 28. PubMed PMID: 26643993.
13: Holdstock L, Meadowcroft AM, Maier R, Johnson BM, Jones D, Rastogi A, Zeig S, Lepore JJ, Cobitz AR. Four-Week Studies of Oral Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor GSK1278863 for Treatment of Anemia. J Am Soc Nephrol. 2016 Apr;27(4):1234-44. doi: 10.1681/ASN.2014111139. Epub 2015 Oct 22. PubMed PMID: 26494831; PubMed Central PMCID: PMC4814173.
14: Thevis M, Milosovich S, Licea-Perez H, Knecht D, Cavalier T, Schänzer W. Mass spectrometric characterization of a prolyl hydroxylase inhibitor GSK1278863, its bishydroxylated metabolite, and its implementation into routine doping controls. Drug Test Anal. 2016 Aug;8(8):858-63. doi: 10.1002/dta.1870. Epub 2015 Sep 11. PubMed PMID: 26361079.
15: Olson E, Demopoulos L, Haws TF, Hu E, Fang Z, Mahar KM, Qin P, Lepore J, Bauer TA, Hiatt WR. Short-term treatment with a novel HIF-prolyl hydroxylase inhibitor (GSK1278863) failed to improve measures of performance in subjects with claudication-limited peripheral artery disease. Vasc Med. 2014 Dec;19(6):473-82. doi: 10.1177/1358863X14557151. Epub 2014 Nov 6. PubMed PMID: 25377872.
16: Andringa KK, Agarwal A. Role of hypoxia-inducible factors in acute kidney injury. Nephron Clin Pract. 2014;127(1-4):70-4. doi: 10.1159/000363669. Epub 2014 Sep 24. Review. PubMed PMID: 25343825.
17: Johnson BM, Stier BA, Caltabiano S. Effect of food and gemfibrozil on the pharmacokinetics of the novel prolyl hydroxylase inhibitor GSK1278863. Clin Pharmacol Drug Dev. 2014 Mar;3(2):109-17. doi: 10.1002/cpdd.83. Epub 2013 Oct 22. PubMed PMID: 27128455.
18: Beuck S, Schänzer W, Thevis M. Hypoxia-inducible factor stabilizers and other small-molecule erythropoiesis-stimulating agents in current and preventive doping analysis. Drug Test Anal. 2012 Nov;4(11):830-45. doi: 10.1002/dta.390. Epub 2012 Feb 24. Review. PubMed PMID: 22362605.
