PVALB

Parvalbumin

Score: 0.330 Price: $0.33 Low Druggability Status: active Wiki: PVALB

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

DEBATES

3D Protein Structure

🧬 PVALB — PDB 4CPR Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.34

Clinical Stage

Phase II

Target Class

Signaling Protein

Safety

0.30

Druggability Analysis

Drug Development0.50

Structural Tractability0.70

Target Class0.50

Safety Profile0.30

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (2 compounds)

1 Approved

Therapeutic Areas:

Alzheimer's disease Schizophrenia Cognitive dysfunction/dementia Gamma oscillation disorders Neuroinflammation Age-related neurodegeneration

Druggability Rationale: PVALB presents low druggability (0.30) as a calcium-binding signaling protein with no known direct druggable mechanism; however, indirect modulation is feasible as evidenced by approved GABA modulators (Diazepam) and phase 2 candidates that target PV+ interneurons through downstream pathways rather than PVALB itself. The low druggability score reflects the challenge of targeting a structural calcium-binding protein directly, though the existing clinical precedent suggests therapeutic benefit through functional modulation of PV+ neuron activity.

Mechanism: No known druggable mechanism

Drug Pipeline (2 compounds)

1 Approved

Known Drugs:

Diazepam (approved) — GABA modulator affecting PV+ interneurons

TPA023 (phase2) — Alpha2/3-selective GABA modulator

Structural Data:

PDB (7) ✓AlphaFold ✓Cryo-EM —

1RJV 1RWY 1S3P 1XVJ 2JWW+2 more

UniProt: P20472

Binding Pocket Analysis:

PVALB contains two canonical EF-hand calcium-binding motifs (identified in available PDB structures at 2.72 Å resolution) that serve as structural rather than druggable pockets; therapeutic targeting may focus on protein-protein interaction surfaces or allosteric sites that modulate calcium-dependent conformational changes affecting interneuron excitability and gamma oscillation generation.

🧬 3D Protein Structure

🧬 PVALB — PDB 4CPR Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

Selectivity challenges arise from PVALB's widespread expression across fast-spiking interneurons and muscle tissue; direct targeting risks off-target effects on skeletal and cardiac muscle. Indirect approaches via GABA-A receptor modulation offer better selectivity for CNS-restricted PV+ interneurons, though achieving neuron-subtype specificity remains challenging.