FG-4592

• CAT Number: I004943
• CAS Number: 808118-40-3
• Molecular Formula: C19H16N2O5
• Molecular Weight: 352.34
• Purity: ≥95%
• Synonyms: Roxadustat; FG-4592
• Target: HIF
• Solubility: DMSO >70 mg/mL Water <1 mg/mL Ethanol <1 mg/mL
• Storage: -20°C
• IUPAC Name: 2-[(4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carbonyl)amino]acetic acid
• 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
• SMILES: CC1=NC(=C(C2=C1C=C(C=C2)OC3=CC=CC=C3)O)C(=O)NCC(=O)O

Roxadustat（Cat No.:I004943）, also known as FG-4592, is an inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase, an enzyme involved in the regulation of cellular responses to low oxygen levels. It is currently undergoing clinical development for the treatment of anemia. By inhibiting HIF prolyl hydroxylase, roxadustat stimulates the production of erythropoietin, a hormone that promotes the production of red blood cells. This mechanism of action makes roxadustat a potential therapeutic option for patients with anemia, including those with chronic kidney disease and chemotherapy-induced anemia.

Reference

1. Adv Ther. 2017 Apr;34(4):848-853. doi: 10.1007/s12325-017-0508-9. Epub 2017 Mar
13.

A New Approach to the Management of Anemia in CKD Patients: A Review on
Roxadustat.

Becker K(1), Saad M(2).
Author information:
(1)St. John/’s University, Jamaica, NY, USA. .
(2)St. John/’s University, Jamaica, NY, USA.

This article informs the reader of the current information available on a novel
therapeutic agent and new class of drug for the treatment of anemia. The data
show promising results for alternative erythropoietin-stimulating agents and
offers a time line of when Phase III data will be available. The information on
this new drug and new drug class will change how nephrologists approach treating
anemia within their patients.

2. Int J Toxicol. 2017 Jan 1:1091581817737232. doi: 10.1177/1091581817737232. [Epub
ahead of print]

Evaluation of the Carcinogenic Potential of Roxadustat (FG-4592), a Small
Molecule Inhibitor of Hypoxia-Inducible Factor Prolyl Hydroxylase in CD-1 Mice
and Sprague Dawley Rats.

Beck J(1), Henschel C(1), Chou J(1), Lin A(1), Del Balzo U(1).
Author information:
(1)1 FibroGen, Inc, San Francisco, CA, USA.

The carcinogenic potential of roxadustat (FG-4592), a novel orally active,
heterocyclic small molecule inhibitor of hypoxia-inducible factor prolyl
hydroxylase (HIF-PH) enzymes in clinical development for treatment of anemia, was
evaluated in CD-1 mice and Sprague Dawley rats. Inhibition of HIF-PH by
roxadustat leads to a rapid increase in cytoplasmic HIF-α concentrations,
followed by translocation of HIF-α to the nucleus and upregulation of
HIF-responsive genes, including erythropoietin. Roxadustat was dosed by oral
gavage 3 times weekly (TIW) for up to 104 weeks in mice at 0, 15, 30, and 60
mg/kg and in rats at 0, 2.5, 5, and 10 mg/kg. Treatment-associated changes in
hematology parameters were consistent with the pharmacologic activity of
roxadustat and included elevations in hematocrit in mice at 30 and 60 mg/kg TIW
and elevations in erythrocyte count, hemoglobin, hematocrit, and red cell
distribution width in rats at 10 mg/kg TIW. No increase in mortality or
neoplastic effects compared with vehicle controls was observed after roxadustat
treatment in either species. No treatment-related nonneoplastic findings were
observed in mice, whereas nonneoplastic microscopic findings in rats were limited
to atrial/aortic thromboses at 10 mg/kg TIW males and bone marrow
hypercellularity in all treated male and female groups, consistent with the
pharmacology of roxadustat. In conclusion, roxadustat administered by oral gavage
to mice and rats TIW for up to 104 weeks resulted in dose-dependent exposure and
hematologic effects with no effect on survival or development of neoplastic
lesions at up to 60 mg/kg in mice and up to 10 mg/kg in rats.