Roxadustat (ASP1517, FG-4592), cas 808118-40-3
Properties of Roxadustat (ASP1517, FG-4592), cas 808118-40-3
Appearance：White to Pale Green Solid
Solubility：DMSO (Slightly), Ethanol (Very Slightly, Heated)
Introduction of Roxadustat (ASP1517, FG-4592), cas 808118-40-3
N-[(4-Hydroxy-1-methyl-7-phenoxy-3-isoquinolinyl)carbonyl]glycine is a hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor used to increase white blood cell levels in blood and hematopoietic progenitor cells in bone marrow.
FG-4592 (also known as ASP1517), 2-(4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carboxamido)acetic acid, is a potent small molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH), an enzyme up-regulating the expression of endogenous human erythropoietin (Epo). It is currently being investigated as an oral treatment for anemia associated with chronic kidney disease (CKD). Unlike other anemia treating agents, erythropoiesis-stimulating agents (ESAs), FG-4592 inhibits HIF, through a distinctive mechanism, by stabilization of HIF. According to previous studies, FG-4592 is capable of correcting and maintaining hemoglobin levels in CKD patients not receiving dialysis and in patients of end-stage renal disease who receives dialysis but do not need intravenous iron supplement.
Roxadustat is a hypoxia-inducible factor prolyl hydroxylase enzyme (HIF-PH) inhibitor (IC50 = 591.4 nM). Roxadustat reduces basal oxygen consumption and increases glycolysis in vitro. It increases hemoglobin levels and stimulates erythropoiesis in vivo. By reducing ACE2 expression, roxadustat reduces the levels of SARS-CoV-2 viral RNA and inhibits entry, replication and secretion of infectious particles in lung epithelial cells. Roxadustat also suppresses hydroxylation and secretion of high molecular weight forms of mannose-binding lectin. The compound suppresses ion currents in pituitary tumor cells (IC50 values for inhibition of peak and late components of delayed rectifier calcium currents are 5.71 and 1.32 μM, respectively).
General tips of Roxadustat (ASP1517, FG-4592), cas 808118-40-3
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.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it
Storage：Refrigerator（-20°C；Stability：≥ 2 years
Handling：Protect from air and moisture
About Packaging of Roxadustat (ASP1517, FG-4592), cas 808118-40-3
1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment
References of Roxadustat (ASP1517, FG-4592), cas 808118-40-3
1) Besarab A, Provenzano R, Hertel J, Zabaneh R, Klaus SJ, Lee T, Leong R, Hemmerich S, Yu KH, Neff TB. Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients. Nephrol Dial Transplant. 2015 Oct;30(10):1665-73.2) Forristal CE, Levesque JP. Targeting the hypoxia-sensing pathway in clinical hematology. Stem Cells Transl Med. 2014 Feb;3(2):135-40.
2) Cases A. The latest advances in kidney diseases and related disorders. Drug News Perspect. 2007 Dec;20(10):647-54.
3）Liu H, et al. Prolyl-4-Hydroxylases Inhibitor Stabilizes HIF-1α and Increases Mitophagy to Reduce Cell Death After Experimental Retinal Detachment. Invest Ophthalmol Vis Sci. 2016 Apr 1;57(4):1807-15. . Yu Y, et al. Hypoxia enhances tenocyte differentiation of adipose-derived mesenchymal stem cells by inducing hypoxia-inducible factor-1α in a co-culture system. Cell Prolif. 2016 Apr;49(2):173-84.
4） Luis Borges. Different modalities of erythropoiesis stimulating agents. Port J Nephrol Hypert 2010; 24(2): 137-145
5） “FibroGen and Astellas announce initiation of phase 3 trial of FG-4592/ASP1517 for treatment of anemia of chronic kidney disease” Fibrogen Press Release. Dec 11 2012
6） “FibroGen announces initiation of phase 2b studies of FG-4592, an oral HIF prolyl hydroxylase inhibitor, for treatment of anemia”
7）Seeley, TW, et al. U.S. Pat. Appl. Publ. 2007, US 20070292433 A1 20071220.