GPX4

Glutathione peroxidase 4

Score: 0.565 Price: $0.57 Low Druggability Status: active Wiki: GPX4

🧠 Neurodegeneration

HYPOTHESES

5

PAPERS

22

KG EDGES

1173

DEBATES

1

3D Protein Structure

🧬 GPX4 — PDB 2OBI Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.41

Clinical Stage

Phase II

Target Class

Enzyme

Safety

0.30

Druggability Analysis

Drug Development0.30

Structural Tractability0.85

Target Class0.85

Safety Profile0.30

Key Metrics

PDB Structures:

24

Known Drugs:

2

Approved:

0

In Clinical Trials:

0

Drug Pipeline (2 compounds)

2 Preclinical

Druggability Rationale: GPX4 demonstrates medium druggability (0.55) with clear structural tractability evidenced by 24 PDB structures at 1.01 Å resolution and active investigation of tool compounds (RSL3, ML210). However, the target's essential cytoprotective function against ferroptosis presents a double-edged challenge: inhibitors show cancer research potential but carry high neurotoxicity risk, while activators require overcoming the enzyme's already-efficient catalytic mechanism and potential off-target effects on related peroxidases.

Mechanism: Small molecule inhibitor or activator of peroxidase activity

Drug Pipeline (2 compounds)

2 Preclinical

Known Drugs:

RSL3 (investigational) — Cancer research tool

ML210 (investigational) — Research tool compound

Structural Data:

PDB (24) ✓AlphaFold ✓Cryo-EM —

2GS3 2OBI 5H5Q 5H5R 5H5S+19 more

UniProt: P36969

🧬 3D Protein Structure

🧬 GPX4 — PDB 2OBI Click to expand interactive 3D viewer

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Selectivity & Safety Considerations

GPX4 selectivity is complicated by structural similarity to other glutathione peroxidases (GPX1-GPX3, GPX5-GPX8), requiring careful ligand design to avoid off-target peroxidase inhibition that could dysregulate redox homeostasis. Tissue-specific expression patterns (particularly high in nervous system and testis) may enable some selectivity advantage through pharmacokinetics, but active site conservation poses inherent selectivity challenges.

3D Protein Structure

PDB: Open in RCSB AlphaFold model

Interactive 3D viewer powered by RCSB PDB / Mol*. Use mouse to rotate, scroll to zoom.

Clinical Trials (10)

Relevant trials from ClinicalTrials.gov

Active

5

Completed

4

Total Enrollment

2,103

By Phase

NA: 3 · PHASE2: 3 · Unknown: 4

Analysis of HIF-1α, MDA, and GPX4 in Peri-Implant Crevicular Fluid Completed

Unknown NCT06863116 n=45

Peri-Implantitis and Peri-implant Mucosi, Hypoxia, Ferroptosis

Sponsor: Ege University | Started: 2023-05-15

Effect of Selenium on Succinylcholine-Induced POM Completed

PHASE2 NCT03476044 n=80

Postoperative Myalgia

Interventions: Placebo, Selenium

Sponsor: Assiut University | Started: 2018-06-01

Identification of Serum Level of Glutathione Peroxidase 4 Not Yet Recruiting

Unknown NCT06554392 n=85

Spondyloarthropathy

Interventions: Blood sample

Sponsor: Assiut University | Started: 2024-09-01

Oxygen-guided Supervised Exercise Therapy Recruiting

NA NCT06003855 n=12

Peripheral Artery Disease

Interventions: Supervised exercise therapy

Sponsor: VA Office of Research and Development | Started: 2023-10-01

Markers of Oxidative Stress in Inflammatory Bowel Diseases: Risk Factors and Implications for a Dietetic Approach Active Not Recruiting

NA NCT04513015 n=155

Inflammatory Bowel Diseases

Interventions: Antioxidant diet, Normal dietetic scheme

Sponsor: Università Politecnica delle Marche | Started: 2019-12-15

Ferroptosis Role in the Pathophysiology of Systemic Lupus Erythematosus Not Yet Recruiting

NA NCT07260942 n=120

Systemic Lupus Erythematosus

Interventions: blood sample

Sponsor: University Hospital, Bordeaux | Started: 2025-12

Association Between Ferroptosis and Epilepsy Completed

Unknown NCT05269901 n=40

Epilepsy

Interventions: SLC7A11, GPX4, P53

Sponsor: Affiliated Hospital of Jiangnan University | Started: 2021-01-20

Sex-specific Association With Kidney Disease Completed

Unknown NCT01810822 n=1396

Diabetic Nephropathy

Sponsor: University of Sao Paulo General Hospital | Started: 1994-05

Linked Hypotheses (2)

Ferroptosis Inhibition for α-Synuclein Neuroprotection0.705

GPX4 Selenopeptide Mimetics as Neuroprotective Ferroptosis Blockade0.680

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

activates (1)

associated with (1)

GPX4→neurodegeneration

co discussed (14)

MMP9→GPX4SLC7A11→GPX4AQP4→GPX4CD38→GPX4C1Q→GPX4

▸ Show 9 more

NAMPT→GPX4GPX4→PLA2G6GPX4→MMP2GPX4→C3GPX4→PLA2G4ACGAS→GPX4GPX4→IL1BGPX4→DNASE2GPX4→STING1

inhibits (1)

interacts with (1)

regulates (2)

Nrf2→GPX4SLC7A11→GPX4

Debate History (1)

Should GPX4 (Glutathione peroxidase 4) be prioritized as a therapeutic target fo2026-04-21