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Prolyl Hydroxylase (PHD)
- Target
- PHD
- Molecular classification
- Enzyme, Dioxygenase, Oxidoreductase, 2-oxoglutarate-dependent dioxygenase, Non-heme iron(II)-dependent dioxygenase
01
Overview
Prolyl hydroxylases (PHDs) are a family of enzymes that catalyze the hydroxylation of proline residues in proteins, primarily collagen and hypoxia-inducible factor alpha (HIFα). This post-translational modification is crucial for collagen stability and cellular oxygen sensing. Inhibitors of PHDs are being developed as therapeutics to stabilize HIFα for the treatment of anemia and other conditions.
- Other names
- Prolyl-4-hydroxylaseProcollagen-proline dioxygenaseEGLN1EGLN2EGLN3P4HAP4HB
02
Mechanism of action
Prolyl hydroxylase inhibitors stabilize HIFα by preventing its hydroxylation, thus blocking its recognition by von Hippel-Lindau protein (pVHL) and subsequent proteasomal degradation. This leads to increased expression of HIF-target genes.
03
Biological functions
Collagen stabilizationCellular oxygen sensingRegulation of HIFPost-translational modificationProtein hydroxylation
04
Disease associations
Connective tissue disordersAnemiaCancerTumor progressionHypoxia-related diseases
05
Safety considerations
Potential for excessive angiogenesisIncreased risk of tumor growthOff-target effects due to overlapping substrate specificityCardiovascular risks
06
Interacting drugs
Prolyl hydroxylase inhibitors
4 more in the full profile.
07
Biomarkers
HIFα levelsErythropoietin (EPO) levelsCollagen hydroxylation levelsProline hydroxylation status in target proteins
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