PLA2G4A

Phospholipase A2 group IVA

Score: 0.600 Price: $0.60 Low Druggability Status: active Wiki: PLA2G4A

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

DEBATES

3D Protein Structure

🧬 PLA2G4A — PDB 1BCI Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.40

Clinical Stage

Phase II

Target Class

Enzyme

Safety

0.50

Druggability Analysis

Drug Development0.30

Structural Tractability0.70

Target Class0.85

Safety Profile0.50

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (1 compounds)

Therapeutic Areas:

Alzheimer's disease Parkinson's disease stroke/ischemic neurodegeneration neuroinflammation traumatic brain injury age-related cognitive decline

Druggability Rationale: PLA2G4A is highly druggable (0.80 score) as an enzyme target with a well-defined catalytic active site suitable for small molecule inhibitors. The existence of tool compounds like arachidonyl trifluoromethyl ketone and high-resolution structural data (2.4 Å PDB 6IEJ) provide validated binding templates for competitive inhibitor design.

Mechanism: Small molecule inhibitor of cytosolic phospholipase A2 enzymatic activity

Drug Pipeline (1 compounds)

Known Drugs:

Arachidonyl trifluoromethyl ketone (tool_compound) — research

Structural Data:

PDB (1) ✓AlphaFold ✓Cryo-EM —

6IEJ

UniProt: P47712

Binding Pocket Analysis:

The catalytic active site accommodates substrate phospholipids and calcium cofactors, with the 2.4 Å resolution structure revealing conserved catalytic residues and substrate-binding grooves typical of serine esterases. Structural data supports design of competitive inhibitors that exploit the phospholipid binding pocket and calcium-dependent conformational dynamics.

🧬 3D Protein Structure

🧬 PLA2G4A — PDB 1BCI Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

Selectivity remains a challenge given the PLA2 family's structural homology; distinguishing PLA2G4A from other Group IVA isoforms and non-selective phospholipase inhibition requires careful active site targeting. Off-target effects on other arachidonic acid-releasing phospholipases may limit therapeutic window.