2008年2月15日 · Oxygen-dependent hydroxylation of hypoxia-inducible factor (HIF)- α subunits by prolyl hydroxylase domain (PHD) proteins signals their polyubiquitination and proteasomal...

The prolyl hydroxylase domain (PHD) / hypoxia-inducible factor (HIF) axis is a critically important oxygen-sensing pathway that mediates tissue adaptation to low oxygen environments primarily via the transcriptional regulation of gene expression.

Hypoxia-inducible factor–prolyl hydroxylase domain inhibitors (HIF-PHIs) are a promising new class of orally administered drugs currently in late-stage global clinical development for the treatment of anemia of chronic kidney disease (CKD).

2025年1月18日 · Hypoxia-inducible factors (HIFs) are key transcription factors mediating the activation of many oxygen-dependent genes. HIF activation occurs in many pathological disease states, including ischemia, anemia, pulmonary hypertension, kidney disease, and …

The hypoxia-inducible factor (HIF) prolyl hydroxylase domain enzymes (PHDs) regulate the stability of HIF protein by post-translational hydroxylation of two conserved prolyl residues in its α subunit in an oxygen-dependent manner.

2024年4月18日 · We investigated clinically used PHD inhibitors and a new selective PHD inhibitor (IOX5), to stabilize HIF-α in AML cells. PHD inhibition compromises AML in a HIF-1α-dependent manner to disable...

In this review, I discuss the process of molecular cloning of HIF and HIF-PH, which explains hypoxia-induced EPO expression; the development of HIF-PH inhibitors that artificially or exogenously activate HIF by inhibiting HIF-PH; and the significance and implications of medical intervention using HIF-PH inhibitors.

2018年8月23日 · Prolyl hydroxylase domain (PHD) enzyme inhibition can stabilize hypoxia-inducible factor (HIF). HIF stabilization also decreases hepcidin, a hormone of hepatic origin, which regulates iron homeostasis.

2019年1月1日 · The links between hypoxia signaling and inflammation are bidirectional: hypoxia may also exacerbate inflammation through activation of inflammatory pathways and effects on immune cell fate and function. The HIF/PHD pathway can also be activated in normoxia in response to inflammatory stimuli.

Cells sense and respond to hypoxia through the activity of the transcription factor HIF (hypoxia-inducible factor) and its regulatory hydroxylases, the prolyl hydroxylase domain enzymes (PHDs). Multiple isoforms of HIFs and PHDs exist, and isoform-selective roles have been identified in …