prolyl hydroxylase


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pro·lyl hy·drox·y·lase

an enzyme that catalyzes the hydroxylation of certain prolyl residues in collagen precursors using molecular oxygen, ferrous ion, ascorbic acid, and α-ketoglutarate; a vitamin C deficiency directly affects the activity of this enzyme; one form of this enzyme (prolyl 4-hydroxylase) synthesizes 4-hydroxyprolyl residues while another produces 3-hydroxyprolyl residues.
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Among them are two long-known collagen prolyl-4-hydroxylases (Myllyharju 2003), the more recently identified FIH-1 (factor inhibiting HIF), and PHD1-3, asparaginyl and prolyl hydroxylases, responsible for HIF-[alpha] protein hydroxylation (Epstein et al.
Using its expertise in the field of tissue fibrosis, in particular with matricellular proteins, such as connective tissue growth factor (CTGF), and matrix assembly enzymes, such as prolyl hydroxylases, FibroGen is now engaged in clinical development of anti-CTGF therapy and prolyl hydroxylase inhibitors for serious unmet medical needs.
today announced data from an ongoing phase 2b dose-finding study of FG-4592, an investigational hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (PHI), for anemia correction and hemoglobin (Hb) maintenance in patients with stage 3 or 4 chronic kidney disease (CKD) not on dialysis.
FG-4592 oral hypoxia-inducible factor prolyl hydroxylase inhibitor corrects anemia in nondialysis CKD patients without IV iron.
Martinelli is responsible for the chemistry, manufacturing, and controls (CMC) development activities for FibroGen's most advanced small molecule clinical candidates, including FG-4592, a first-in-class hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (PHI), in phase 2b development for the treatment of anemia associated with chronic kidney disease.
Using its expertise in the field of tissue fibrosis, in particular with matricellular proteins such as CTGF, and matrix assembly enzymes such as prolyl hydroxylases, FibroGen now is engaged in clinical development of anti-CTGF therapy and prolyl hydroxylase inhibitors for serious unmet medical needs.
Frost, who joined FibroGen at the beginning of the year, is focused on leading global regulatory activities for the company's most advanced clinical candidates, including FG-4592, a first-in-class small molecule hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (PHI), in phase 2b development for the treatment of anemia associated with chronic kidney disease (CKD), and FG-3019, a human monoclonal antibody that inhibits the activity of connective tissue growth factor (CTGF), in phase 2 development for the treatment of fibrotic diseases and pancreatic cancer.
today announced proof-of-principle for oral anemia therapy FG-4592, a hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (PHI), in end-stage renal disease (ESRD) patients receiving hemodialysis.
Preliminary results from a randomized, single-blind, placebo-controlled trial of FG-4592, a novel hypoxia inducible factor prolyl hydroxylase inhibitor, in subjects with CKD anemia (2007) J Am Soc Nephrol 18:763
FG-4592 is a novel, first-in-class hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (PHI) that works through stabilization of HIF, a mechanism distinct from that of current anemia therapy using erythropoiesis-stimulating agents (ESAs).
The new findings show that activation of hepatic erythropoietin production using systemically delivered siRNA targeting EglN prolyl hydroxylases leads to improved red blood cell production in pre-clinical models of anemia.
Lastly, in a poster titled "Liver Specific Delivery of siRNA Targeting EGLN Prolyl Hydroxylases Activates Hepatic Erythropoietin Production and Stimulates Erythropoiesis," Alnylam scientists and collaborators at the Dana-Farber Cancer Institute and the Massachusetts Institute of Technology (MIT) highlighted the potential of RNAi therapeutics targeting liver-expressed egl nine homolog (EGLN) prolyl hydroxlase genes to promote effective and durable erythropoiesis.