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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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Purity: ≥98%
Daprodustat (formerly known as GSK1278863; Duvroq) is a novel orally bioavailable hypoxia-inducible factor prolyl hydroxylase (HIF-PHI) inhibitor that has been approved for treatment of anemia associated with CKD/chronic kidney disease. GSK1278863 induced an effective EPO response and stimulated non-EPO mechanisms for erythropoiesis in anemic non-dialysis-dependent and dialysis-dependent patients with CKD. In a clinical study conducted in healthy Japanese and Caucasian subjects to evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and safety of GSK1278863, GSK1278863 was found to be well tolerated, with dose-proportional increases in exposure observed in both groups. There was no evidence of ethnic differences between Japanese and Caucasian with regard to PK or PD. In Feb 2023, the U.S. FDA approved Jesduvroq tablets (daprodustat) as the first oral treatment for anemia (decreased number of red blood cells) caused by CKD/chronic kidney disease in adults on dialysis.
Targets |
HIF-PH/hypoxia-inducible factor prolyl hydroxylase
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ln Vitro |
GSK1278863 is a small-molecule PHI that is taken orally that promotes the production of endogenous EPO and induces efficient erythropoiesis[1]. It has been demonstrated that GSK1278863 raises erythropoietin levels, which raises hemoglobin, hematocrit, and red blood cell counts[2].
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ln Vivo |
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Cell Assay |
Decreased erythropoietin (EPO) production, shortened erythrocyte survival, and other factors reducing the response to EPO contribute to anemia in patients who have a variety of underlying pathologies such as chronic kidney disease. Treatment with recombinant human EPO (rHuEPO) at supraphysiologic concentrations has proven to be efficacious. However, it does not ameliorate the condition in all patients, and it presents its own risks, including cardiovascular complications. The transcription factors hypoxia-inducible factor (HIF) 1α and HIF2α control the physiologic response to hypoxia and invoke a program of increased erythropoiesis. Levels of HIFα are modulated by oxygen tension via the action of a family of HIF-prolyl hydroxylases (PHDs), which tag HIFα for proteasomal degradation. Inhibition of these PHDs simulates conditions of mild hypoxia, leading to a potentially more physiologic erythropoietic response and presenting a potential alternative to high doses of rHuEPO. Here we describe the discovery and characterization of GSK1278863 [2-(1,3-dicyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamido) acetic acid], a pyrimidinetrione-glycinamide low nanomolar inhibitor of PHDs 1-3 that stabilizes HIFα in cell lines, resulting in the production of increased levels of EPO. [3]
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Animal Protocol |
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References |
[1]. Brigandi RA, et al. 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
[2]. Hara K, et al. 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. [3]. 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. |
Molecular Formula |
C19H27N3O6
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Molecular Weight |
393.43
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Exact Mass |
393.18997
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Elemental Analysis |
C, 58.00; H, 6.92; N, 10.68; O, 24.40
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CAS # |
960539-70-2
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Related CAS # |
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Appearance |
White to off-white solid
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LogP |
0.86
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tPSA |
124.09
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SMILES |
O=C(O)CNC(C(C(N1C2CCCCC2)=O)C(N(C3CCCCC3)C1=O)=O)=O
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InChi Key |
RUEYEZADQJCKGV-UHFFFAOYSA-N
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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)
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Chemical Name |
(1,3-dicyclohexyl-2,4,6-trioxohexahydropyrimidine-5-carbonyl)glycine
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Synonyms |
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.35 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.35 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.5417 mL | 12.7087 mL | 25.4175 mL | |
5 mM | 0.5083 mL | 2.5417 mL | 5.0835 mL | |
10 mM | 0.2542 mL | 1.2709 mL | 2.5417 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.