P2RX7

P2X purinoreceptor 7

Score: 0.680 Price: $0.68 High Druggability Status: active Wiki: P2RX7

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

155

DEBATES

3D Protein Structure

🧬 P2RX7 — PDB 5U1L Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

High

Score: 0.80

Clinical Stage

Phase II

Target Class

Ion Channel

Safety

0.60

Druggability Analysis

Drug Development0.30

Structural Tractability0.85

Target Class0.85

Safety Profile0.60

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (2 compounds)

2 Preclinical

Therapeutic Areas:

Neuroinflammation Neurodegenerative diseases Depression and mood disorders Inflammatory diseases Microglial activation disorders Alzheimer's disease Neuropathic pain

Druggability Rationale: P2X7 is highly druggable due to its well-characterized ATP-binding pocket, extensive structural data (24 PDB structures with sub-angstrom resolution), and proven clinical precedent with multiple selective antagonists in Phase 2 trials. The ion channel architecture provides a clearly defined ligand-binding site, and the high druggability score (0.80) reflects established chemical matter and successful target validation in inflammatory and neuropsychiatric indications.

Mechanism: Selective P2X7 receptor antagonists blocking ATP-gated ion channel

Drug Pipeline (2 compounds)

2 Preclinical

Known Drugs:

A-804598 (investigational) — inflammatory diseases

JNJ-54175446 (investigational) — depression

Structural Data:

PDB (24) ✓AlphaFold ✓Cryo-EM —

5U1L 5U1U 5U1V 5U1W 5U1X+19 more

UniProt: Q0IJ51

Binding Pocket Analysis:

P2X7 possesses a well-defined orthosteric ATP-binding pocket located at subunit interfaces, accessible through structural studies including cryo-EM data and AlphaFold modeling. Allosteric binding sites have also been identified, offering opportunities for selective antagonism; the extracellular vestibule and transmembrane regions provide distinct pharmacophoric opportunities beyond classical ATP-competitive inhibition.

Selectivity & Safety Considerations

P2X7 selectivity over closely related P2X family members (P2X1-P2X6) is achievable but requires careful structural optimization, as antagonists may show cross-reactivity with other purinergic receptors. The unique C-terminal domain and specific ATP-binding pocket geometry of P2X7 provide selectivity advantages, though off-target effects on other ATP-sensing proteins should be monitored during development.