Molecular Weight (MW)

352.34

Formula

C19H16N2O5

CAS No.

808118-40-3

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 70 mg/mL (198.7 mM)

Water: <1 mg/mL

Ethanol: <1 mg/mL

Solubility (In vivo)

5% DMSO+50% PEG 300+ddH2O: 11mg/mL

Synonyms

Roxadustat; ASP1517; ASP 1517; ASP-1517; FG-4592; FG4592; FG-4592;

Chemical Name: (4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carbonyl)glycine

InChi Key: YOZBGTLTNGAVFU-UHFFFAOYSA-N

InChi Code: InChI=1S/C19H16N2O5/c1-11-15-9-13(26-12-5-3-2-4-6-12)7-8-14(15)18(24)17(21-11)19(25)20-10-16(22)23/h2-9,24H,10H2,1H3,(H,20,25)(H,22,23)

SMILES Code: O=C(O)CNC(C1=C(O)C2=C(C(C)=N1)C=C(OC3=CC=CC=C3)C=C2)=O

In Vitro

In vitro activity: FG-4592 is an oral inhibitor of hypoxia inducible factor (HIF) prolyl hydroxylase currently in clinical development for the treatment of anemia. FG-4592 stabilizes the activities of HIF, a cytosolic transcription factor, leading to activation of the genes associated with erythropoiesis, including erythropoietin and enzymes involved in iron metabolism.

Kinase Assay: FG-4592 (also known as ASP1517 and Roxadustat) is a novel, oral and potent small molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH), an enzyme up-regulating the expression of endogenous human erythropoietin (Epo). Roxadustat induces EPO production and stimulates erythropoiesis.

Cell Assay: FG-4592 showed significant protection effect against the TBHP-induced cell death. Cell line used: PC-12 cells. The left eye of each rat is retro-orbitally injected with 25 mg/kg FG-4592 every 2 days, and an equal volume of 20% DMSO diluted with 0.9% NaCl is administrated with retro-orbital injection and served as the control. The retinae (attached, 1 day, 3 days, 5 days, and 7 days after RD) are homogenized and lysed with buffer containing 50 mM hydroxymethyl(Tris)-aminomethane(HCl), 150 mM NaCl, 1% Triton X-100, 1% sodium deoxycholate, 0.1% SDS, and a protease inhibitor tablet. Samples are run on 8% to 12% 2-hydroxyethyl (Bis)-hydroxymethyl (Tris) gel electrophoresis and transferred onto polyvinylidene difluoride (PVDF) membranes (0.2-mm pores). After blocking with 3% nonfat dried milk, the membranes are incubated overnight with primary antibody HIF-1α, LC3, BNIP3, autophagy-related gene 5 (Atg5), and β-actin. The blotted membranes are then incubated for 60 minutes at room temperature with a horseradish peroxidase (HRP)-labeled secondary antibody. Immunoreactive bands are visualized by enhanced chemiluminescence (ECL) and detected with an Amersham Imager 600. A minimum of three rats are used for each condition.

In Vivo

In a mouse model of spinal cord injury, FG-4592 administration improved recovery and increased the survival of neurons in spinal cord lesions

Animal model

Mouse model of spinal cord injury

Formulation & Dosage

50mg/kg/day; i.p.; for 7 days

References

Brain Res. 2016 Feb 1;1632:19-26;