ALOX5

5-lipoxygenase

Score: 0.646 Price: $0.65 Medium Druggability Status: active Wiki: ALOX5

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

DEBATES

3D Protein Structure

🧬 ALOX5 — 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:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (1 compounds)

1 Approved

Therapeutic Areas:

Asthma and allergic airway disease Neuroinflammation and neurodegeneration Alzheimer's disease Parkinson's disease Multiple sclerosis Inflammatory bowel disease Rheumatoid arthritis

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 Å) 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) — Asthma (repurposing potential)

Structural Data:

PDB (9) ✓AlphaFold ✓Cryo-EM —

3O8Y 3V92 3V98 3V99 6N2W+4 more

UniProt: A0A087X109

Binding Pocket Analysis:

ALOX5 possesses a well-characterized catalytic iron-binding pocket within the active site, accessible through the 1.98 Å resolution structures (PDB 3O8Y, 3V92-99, 6N2W). The binding pocket accommodates competitive inhibitors that chelate the catalytic iron and block substrate access, providing a defined target for structure-based optimization of improved scaffolds beyond zileuton.

🧬 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.