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Target intelligence / Profile preview
Proline Hydroxylase (PHD)
- Target
- PHD
- Molecular classification
- Enzyme, Dioxygenase
01
Overview
Proline hydroxylase is a family of enzymes that catalyze the hydroxylation of proline residues in proteins, primarily collagen and hypoxia-inducible factor (HIF) alpha subunits. This modification is critical for collagen stability and cellular oxygen sensing. Specifically, prolyl hydroxylase domain proteins (PHDs or EGLNs) regulate cellular responses to oxygen levels by modifying HIF-alpha transcription factors. Inhibition of PHDs stabilizes HIF-alpha, mimicking hypoxic conditions and promoting erythropoiesis and angiogenesis.
- Other names
- Prolyl hydroxylase domain-containing proteinEGLN
02
Mechanism of action
Inhibition of proline hydroxylation, leading to HIF stabilization and activation of hypoxic response genes.
03
Biological functions
Collagen biosynthesisOxygen sensingRegulation of Hypoxia-Inducible Factor (HIF)Post-translational modification
04
Disease associations
CancerAnemiaIschemiaFibrosis
05
Safety considerations
Potential for off-target effects due to structural similarity with other 2-oxoglutarate-dependent dioxygenasesRisk of erythrocytosis (excessive red blood cell production) with PHD inhibitors
06
Interacting drugs
IOX2
5 more in the full profile.
07
Biomarkers
HIF-alpha levelsErythropoietin (EPO) levels
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