LOXL1-4

Lysyl oxidase-like 1-4

Score: 0.490 Price: $0.49 Low Druggability Status: active Wiki: LOXL1-4

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

DEBATES

3D Protein Structure

🔮 LOXL1-4 — AlphaFold Q08397 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.33

Clinical Stage

Phase II

Target Class

Enzyme

Safety

0.50

Druggability Analysis

Drug Development0.35

Structural Tractability0.30

Target Class0.85

Safety Profile0.50

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (3 compounds)

1 Phase II · 2 Preclinical

Therapeutic Areas:

Neurodegenerative diseases (Alzheimer's disease, Parkinson's disease) Blood-brain barrier dysfunction Neuroinflammation Cerebral amyloid angiopathy Stroke and ischemic brain injury Fibrosis and extracellular matrix remodeling diseases

Druggability Rationale: LOXL1-4 demonstrates medium druggability (0.50) despite lacking crystal structures, supported by the advancement of small molecule inhibitors (PXS-5153A) and monoclonal antibodies (Simtuzumab) into preclinical and Phase 2 stages. The copper-dependent catalytic domain presents a tractable binding pocket for small molecule inhibition, though the absence of PDB structures and limited structural data somewhat constrain rational drug design efforts.

Mechanism: Small molecule enzyme inhibitors targeting the catalytic domain

Drug Pipeline (3 compounds)

1 Phase II · 2 Preclinical

Known Drugs:

BAPN (research_tool)

PXS-5153A (preclinical)

Simtuzumab (phase_2)

Structural Data:

PDB —AlphaFold ✓Cryo-EM —

Binding Pocket Analysis:

The catalytic domain accommodates copper cofactors and substrate-binding residues typical of amine oxidases, though detailed pocket geometry remains uncharacterized without experimental crystal structures; AlphaFold predictions provide computational models that could guide initial docking studies and structure-activity relationship optimization around the lysine oxidation mechanism.

🔮 Predicted Protein Structure (AlphaFold)

🔮 LOXL1-4 — AlphaFold Q08397 Click to expand interactive 3D viewer

AI-predicted structure from AlphaFold EBI | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Selectivity & Safety Considerations

Selectivity among the four LOXL isoforms (LOXL1-4) remains a significant challenge given their structural homology and overlapping catalytic mechanisms, requiring careful optimization to avoid off-target effects on the canonical LOX enzyme. Achieving isoform-selective inhibition will be critical for reducing potential compensatory pathway activation and systemic side effects related to collagen crosslinking in peripheral tissues.