| Daprodustat(GSK1278863)HIF-prolyl hydroxylase inhibitor |
Sample solution is provided at 25 µL, 10mM.
Nature.2017 Jan 19;541(7637):417-420.
Nature.2018 Nov;563(7731):407-411.Nature.2018 Jun 13.Nature.2018 Jun 27.Nature.2018 Mar 29;555(7698):673-677.Nature.2017 Sep 7;549(7670):96-100.Nature.2016 Apr 21;532(7599):398-401.
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- Purity = 98.87%
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Chemical structure
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| Cas No. | 960539-70-2 | SDF | Download SDF |
| Chemical Name | 2-(1,3-dicyclohexyl-2,4,6-trioxohexahydropyrimidine-5-carboxamido)acetic acid | ||
| Canonical SMILES | O=C(O)CNC(C(C(N1C2CCCCC2)=O)C(N(C1=O)C3CCCCC3)=O)=O | ||
| Formula | C19H27N3O6 | M.Wt | 393.43 |
| Solubility | ≥7.86mg/mL in DMSO with gentle warming | Storage | Store at -20°C |
| Physical Appearance | A solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
Daprodustat (GSK1278863) is a HIF-prolyl hydroxylase inhibitor.
Hypoxia stimulates erythropoietin (EPO) release through accumulation of hypoxia-inducible factor 1α (HIF-1α), resulting in an increase of erythrocyte production by the bone marrow. HIF-prolyl hydroxylase inhibitors have been used to selectively activate the PHD-signaling pathway, leading to the stabilization of HIFα subunits, which can affect the transcription of HIF-responsive genes.
In vitro: In-vitro biotransformation data indicated that GSK1278863 was primarily metabolized by CYP2C8 [1].
In vivo: Currently, there is no animal in vivo data published.
Clinical trial: Previous study found that in both Japanese and Caucasian subjects GSK1278863 showed dose-proportional increases in AUCinf, with a 1.3-1.5-fold higher exposure seen in Japanese relative to Caucasians. Such exposure difference could be mainly explained by the observed differences in body weights. Statistically significant increases in erythropoietin, vascular endothelial growth factor (VEGF) and reticulocyte counts were observed in Japanese subjects as compared to placebo. In Caucasians, erythropoietin and VEGF levels were increased in response to the 100 mg dose. Moreover, drug-related adverse events, sucha as headache and abdominal pain, were reported in three Japanese subjects, whereas, headache was reported in three Caucasians [1]. A 28-day, phase 2A, randomized trial showed that GSK1278863 induced an effective EPO response and stimulated non-EPO mechanisms for erythropoiesis in anemic non-dialysis-dependent and dialysis-dependent patients with CKD [2].
References:[1] 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.[2] Brigandi RA,Johnson B,Oei C,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.
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