The enzymes involved are prolyl hydroxylases
and lysyl hydroxylase and the reactions require [O.
Berchner-Pfannschmidt, "Role of reactive oxygen species in the regulation of HIF-1 by prolyl hydroxylase
2 under mild hypoxia," Free Radical Research, vol.
Cellular oxygen sensing: crystal structure of hypoxia-inducible factor prolyl hydroxylase
(PHD2)," Proceedings of the National Academy of Sciences of the United States of America, vol.
A Rieske-type [2Fe-2S] cluster serves as an electron-transferring cofactor, and a mononuclear iron site is the putative site for substrate oxygenation, similar to that predicted in prolyl hydroxylases
domain (PHD) enzymes] (Batie and Ballou 1990).
FG-4592/ASP1517 is an inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase
(a "HIF-PHI"), belonging to a new class of anemia therapeutic agents.
According to the companies, Roxadustat is a hypoxia-inducible factor prolyl hydroxylase
inhibitor (HIF-PHI) that acts by stimulating the body's natural pathway of red blood cell production, or erythropoiesis.
The study was designed to compare FG-4592 , an investigational hypoxia-inducible factor (HIF) prolyl hydroxylase
inhibitor (PHI), with an active comparator (epoetin ) in patients with end-stage renal disease (ESRD) receiving hemodialysis, whose hemoglobin (Hb) levels were previously maintained with intravenous (IV) epoetin and IV iron supplementation.
The product is aimed at stabilising hypoxia inducible factor, a transcription factor that regulates the expression of genes involved with red blood cell production in response to changes in oxygen levels, by inhibiting the HIF prolyl hydroxylase
today announced preliminary clinical findings from an ongoing open-label Phase 2 study demonstrating the safety and efficacy of FG-4592, investigational oral hypoxia-inducible factor (HIF) prolyl hydroxylase
inhibitor (PHI), in the correction of anemia in patients with end-stage renal disease who recently started dialysis with no iron, with oral iron, or with intravenous (IV) iron supplementation.
today announced that two abstracts relating to FG-4592, its oral hypoxia-inducible factor prolyl hydroxylase
inhibitor (HIF-PHI) clinical candidate for the treatment of anemia in chronic kidney disease, have been accepted for oral and poster presentations at the American Society of Nephrology (ASN) Kidney Week 2012.
FibroGen has applied its expertise in the field of tissue fibrosis - with matricellular proteins, such as connective tissue growth factor (CTGF), and with matrix assembly enzymes, such as prolyl hydroxylases
- to the clinical development of anti-CTGF agents and prolyl hydroxylase
inhibitors in therapies meeting serious unmet medical needs.
today announced preliminary clinical findings from two ongoing, open-label phase 2 studies demonstrating that FG-4592, its investigational oral hypoxia-inducible factor (HIF) prolyl hydroxylase
inhibitor (PHI) therapy for anemia, reduced blood pressure in hypertensive patients, reduced cholesterol levels, and improved the ratio of HDL to LDL in lipid profiles, in patients with chronic kidney disease (CKD).