
Characterization of Different Isoforms of the HIF Prolyl Hydroxylase Biochemj
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People also ask
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What drugs are HIF inhibitors?
HIF stabilizers restore production of erythropoietin and also improve iron metabolism by reducing hepcidin levels. There are at least 5 HIF prolyl hydroxylase inhibitors (HIF-PHIs) currently being evaluated in clinical trials: roxadustat, daprodustat, vadadustat, molidustat, and enarodustat.
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What are HIF inhibitors in CKD?
HIF-PHIs reversibly inhibit HIF-PHD dioxygenases, which belong to a larger family of enzymes that utilize molecular oxygen and 2-oxoglutarate for hydroxylation. HIF-PHIs are currently in advanced global clinical development for anemia management in patients with CKD.
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What are the cofactors of prolyl hydroxylase?
HIF-prolyl hydroxylases (HPHs),6 also referred to as prolyl hydroxylase domain (PHD) proteins,7 form an evolutionarily conserved subfamily of dioxygenases that uses oxygen and 2-oxoglutarate (2-OG) as co-substrates, and iron and ascorbate as cofactors.
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What are HIF drugs for anemia?
HIF-PHIs treat anemia by stabilizing hypoxia-inducible factor (HIF), thereby stimulating endogenous erythropoietin production. Additionally, HIF-PHIs also affect the iron metabolism pathway via effects on hepcidin and iron transport proteins.
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What are the different types of HIF?
Members of the HIF gene family encode both alpha and beta subunits which generally form functional heterodimers to regulate transcription [15]. In humans there are three paralogs of the HIF-α subunit (HIF-1α, HIF-2α/EPAS, HIF-3α) and two paralogs of the HIF-β subunit (ARNT, ARNT2).
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What are HIF stabilizers?
HIF stabilizers promote the production of RBCs (erythropoiesis) by increasing the hormone erythropoietin. Erythropoietin is produced primarily by the kidneys in response to the low oxygen level in the blood. Thus, HIF stabilizers improve iron availability to the cells.
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What is the function of HIF-prolyl hydroxylase?
HIF-prolyl hydroxylases (PHs) are molecules that constitute the core molecular mechanism of detecting a decrease in the partial pressure of oxygen, or hypoxia, in the cells; they can be called oxygen sensors.
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What are HIF PH inhibitors drugs?
Three HIF-PHI drugs are in the final stages of development at the time of this writing; roxadustat, vadadustat, and daprodustat in the United States. All work to inhibit HIF-PHs, allowing HIF to be stabilized.
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