ALOX5

5-lipoxygenase

Score: 0.564 Price: $0.56 Medium Druggability Status: active Wiki: ALOX5
๐Ÿง  Neurodegeneration
HYPOTHESES
1
PAPERS
31
KG EDGES
74
DEBATES
1

3D Protein Structure

🧬 ALOX5 โ€” PDB 3O8Y Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability
Medium
Score: 0.49
Clinical Stage
Approved
Target Class
Enzyme
Safety
0.70
Druggability Analysis
Drug Development0.75
Structural Tractability0.70
Target Class0.85
Safety Profile0.70
Key Metrics
PDB Structures:
9
Known Drugs:
1
Approved:
1
In Clinical Trials:
0
Drug Pipeline (1 compounds)
1 Approved
Druggability Rationale: ALOX5 is highly druggable (0.90 score) as a validated enzyme target with a well-characterized active site, demonstrated by 9 available crystal structures and the FDA-approved drug zileuton. The high-resolution structural data (1.98 ร…) and multiple PDB complexes provide excellent templates for structure-based drug design, enabling optimization of potent and selective small molecule inhibitors targeting leukotriene synthesis.
Mechanism: Small molecule inhibitors blocking leukotriene synthesis
Drug Pipeline (1 compounds)
1 Approved
Known Drugs:
Zileuton (approved) โ€” Asthma (repurposing potential)
Structural Data:
PDB (9) โœ“AlphaFold โœ“Cryo-EM โ€”
3O8Y3V923V983V996N2W+4 more
UniProt: A0A087X109

🧬 3D Protein Structure

🧬 ALOX5 — PDB 3O8Y Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

ALOX5 selectivity is achievable due to distinct structural features separating it from other lipoxygenase isoforms (ALOX12, ALOX15); however, off-target lipoxygenase activity should be monitored given the mechanistic overlap within the family. Zileuton's clinical validation demonstrates that selective ALOX5 inhibition is achievable without prohibitive cross-reactivity.

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 (7)

Relevant trials from ClinicalTrials.gov

Active
0
Completed
6
Total Enrollment
302
By Phase
PHASE1: 3 ยท PHASE2: 2 ยท PHASE4: 2
Single Dose Bronchodilatory Study in Asthma Completed
PHASE4 NCT01805687 n=25
Asthma
Interventions: Zileuton extended release
Sponsor: Cornerstone Therapeutics Inc. | Started: 2013-03
Zileuton and Exhaled Nitric Oxide in Asthmatics Completed
PHASE4 NCT00575861 n=19
Asthma
Interventions: zileuton
Sponsor: Gelb, Arthur F., M.D. | Started: 2005-09
PF-04191834 Single Dose Bronchodilatory Study In Asthma. Completed
PHASE2 NCT00723021 n=15
Asthma
Interventions: PF-04191834, PF-04191834, PF-04191834
Sponsor: Pfizer | Started: 2008-07
Safety Study of Zileuton Injection in Patients With Asthma Completed
PHASE1 NCT00299065 n=60
Asthma
Interventions: Zileuton injection
Sponsor: Critical Therapeutics | Started: 2006-01
Trial of Zileuton CR in Children and Adults With Sickle Cell Disease Completed
PHASE1 NCT01136941 n=9
Sickle Cell Disease
Interventions: Zileuton
Sponsor: Children's Hospital Medical Center, Cincinnati | Started: 2010-09
Zileuton With or Without Celecoxib As Chemopreventive Agents in Smokers Completed
PHASE1 NCT01021215 n=84
Tobacco Use Disorder
Interventions: Zileuton, Celecoxib, laboratory biomarker analysis
Sponsor: National Cancer Institute (NCI) | Started: 2010-05
Study of Oral Zileuton in the Treatment of Moderate to Severe Facial Acne Vulgaris Unknown
PHASE2 NCT00098358 n=90
Acne Vulgaris
Interventions: Zileuton
Sponsor: Critical Therapeutics | Started: 2004-11

Linked Hypotheses (1)

Mitochondrial SPM Synthesis Platform Engineering0.647

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Portfolio 0.65 (25%) Druggability 0.49 (20%) Evidence 0.50 (20%) Safety 0.70 (15%) Competitive 0.40 (10%) Connectivity 0.60 (10%) 0.564 composite

Knowledge Graph (20)

activates (12)

ALOX5HMOX1ALOX5ALOX15ALOX5ALOX12ALOX5NFE2L2ALOX5FER
▸ Show 7 more
HMOX1ALOX5ALOX12ALOX5ALOX15ALOX5HK2ALOX5ALOX5ACSL4FERALOX5NFE2L2ALOX5

co discussed (7)

BMAL1ALOX5CLOCKALOX5TFRCALOX5GPR37ALOX5CMKLR1ALOX5
▸ Show 2 more
ALOX12ALOX5BCL2L1ALOX5

contributes to (1)

ALOX5ALOX12

Debate History (1)

Should ALOX5 (5-lipoxygenase) be prioritized as a therapeutic target for neurode2026-04-21