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Prolyl Hydroxylase Domain Protein 2 (PHD2)

Target: PHD2
Molecular classification: Enzyme, Dioxygenase

Overview

PHD2 is a key oxygen sensor and enzyme that regulates the stability of HIF-alpha subunits through proline hydroxylation. Under normal oxygen conditions, PHD2 hydroxylates HIF-alpha, leading to its degradation. In hypoxia, PHD2 activity is reduced, resulting in HIF-alpha accumulation and activation of transcriptional programs that promote adaptation to low oxygen levels. PHD2 also functions as an intracellular manganese sensor.

Other names: EGLN1

Mechanism of action

Inhibition of PHD2 leads to HIF-alpha stabilization and increased transcription of HIF target genes.

Biological functions

Oxygen homeostasisRegulation of erythropoiesisHypoxia responseManganese sensing

Disease associations

CancerAnemiaIschemic diseasesCardiovascular disease

Safety considerations

Potential for off-target effects due to homology with other PHDsUnintended consequences of broad HIF activation

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