Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0192)
Name
Roxadustat
Synonyms
Roxadustat; FG-4592; 808118-40-3; FG4592; Roxadustat (FG-4592); ASP1517; ASP 1517; N-[(4-Hydroxy-1-methyl-7-phenoxy-3-isoquinolinyl)carbonyl]glycine; Roxadustat [USAN:INN]; UNII-X3O30D9YMX; X3O30D9YMX; 2-[(4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carbonyl)amino]acetic acid; Glycine, N-[(4-hydroxy-1-methyl-7-phenoxy-3-isoquinolinyl)carbonyl]-; ASP-1517; FG 4592; CHEMBL2338329; (((4-Hydroxy-1-methyl-7-phenoxyisoquinolin-3-yl)carbonyl)amino)acetic acid; (4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carbonyl)glycine; N-[(4-hydroxy-1-methyl-7-phenoxyisoquinolin-3-yl)carbonyl]glycine; Evrenzo; 2-(4-hydroxy-1-Methyl-7-phenoxyisoquinoline-3-carboxaMido)acetic acid; n-((4-hydroxy-1-methyl-7-phenoxy-3-isoquinolinyl)carbonyl)glycine; [[(4-Hydroxy-1-methyl-7-phenoxyisoquinolin-3-yl)carbonyl]amino]acetic Acid; 2-[(1-methyl-4-oxidanyl-7-phenoxy-isoquinolin-3-yl)carbonylamino]ethanoic acid; roxadustatum; FG-4592 (ASP1517); GLYCINE, N-((4-HYDROXY-1-METHYL-7-PHENOXY-3-ISOQUINOLINYL)CARBONYL)-; 8HO; Evrenzo (TN); Fg-4592[roxadustat]; ROXADUSTAT [INN]; ROXADUSTAT [JAN]; ROXADUSTAT [USAN]; Roxadustat(FG-4592); ROXADUSTAT [WHO-DD]; MLS006010023; Roxadustat (JAN/USAN/INN); SCHEMBL523705; GTPL8454; DTXSID60230644; EX-A390; CHEBI:132774; YOZBGTLTNGAVFU-UHFFFAOYSA-N; BCPP000230; HMS3654M03; AMY16514; BCP02523; BDBM50431015; FG-4592,ASP1517; MFCD20040519; s1007; AKOS026674331; BCP9000684; CCG-268052; CS-1094; DB04847; SB16615; NCGC00346527-01; NCGC00346527-07; AC-31003; AS-17052; HY-13426; SMR004701207; SW219900-1; D10593; J-522733; Q27088611; 2-[[4-hydroxy-1-methyl-7-(phenoxy)isoquinoline-3-carbonyl]amino]acetic acid; N-[(4-Hydroxy-1-methyl-7-phenoxy-3-isoquinolinyl)carbonyl]-glycine, Roxadustat

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Status
Phase 3
Drug Type
Small molecular drug
Structure
Formula
C19H16N2O5
IUPAC Name
2-[(4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carbonyl)amino]acetic acid
Canonical SMILES
CC1=C2C=C(C=CC2=C(C(=N1)C(=O)NCC(=O)O)O)OC3=CC=CC=C3
InChI
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)
InChIKey
YOZBGTLTNGAVFU-UHFFFAOYSA-N
PubChem CID
11256664
TTD Drug ID
D03YKE
Full List of Ferroptosis Target Related to This Drug
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Kidney injury ICD-11: NB92
 Disease Info 
Responsed Regulator RAC-alpha serine/threonine-protein kinase (AKT1) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
PI3K-Akt signaling pathway hsa04151
Cell Process Cell ferroptosis
In Vitro Model mRTs (Mouse renal tissues)
In Vivo Model
C57BL/6 male mice, 6 to 8 weeks old, were purchased from Liaoning Changsheng Biotechnology Co. (Liaoning, China). The animal experiment was conducted in three parts. In the first part, mice were randomly divided into 4 groups (n = 12/group): (1) control group that received an intraperitoneal injection of saline, (2) FG-4592 group that received intraperitoneal injection of FG-4592 once (10 mg/kg, dissolved in DMSO at 50 mg/ml and then further diluted in sterile phosphate-buffered saline to 1 mg/ml), (3) FA group that received intraperitoneal injection of a single dose of FA (250 mg/kg, dissolved in 0.3 M sodium bicarbonate), and (4) FA + FG-4592 group that received FG-4592 two days prior to FA single-dose injection. Kidney specimens and blood samples were collected on the second day (n = 6/group) and the fourteenth day (n = 6/group) after FA injection for further examination. In the second part, mice were treated with a ferroptosis inhibitor (Fer-1). In the third part, mice were treated with a PI3K inhibitor (wortmannin).

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Response regulation Roxadustat (FG-4592) pretreatment is achieved mainly by decreasing ferroptosis at the early stage of FA-induced kidney injury via Akt/GSK-3-mediated Nrf2 activation, which retards the fibrosis progression.
References
Ref 1 Pretreatment with Roxadustat (FG-4592) Attenuates Folic Acid-Induced Kidney Injury through Antiferroptosis via Akt/GSK-3/Nrf2 Pathway. Oxid Med Cell Longev. 2020 Jan 20;2020:6286984. doi: 10.1155/2020/6286984. eCollection 2020.