PVALB

Parvalbumin

Score: 0.335 Price: $0.33 Low Druggability Status: active Wiki: PVALB

🧠 Neurodegeneration

HYPOTHESES

1

PAPERS

0

KG EDGES

24

DEBATES

1

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:

7

Known Drugs:

2

Approved:

1

In Clinical Trials:

1

Drug Pipeline (2 compounds)

1 Approved

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

🧬 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.

3D Protein Structure

PDB: Open in RCSB AlphaFold model

Interactive 3D viewer powered by RCSB PDB / Mol*. Use mouse to rotate, scroll to zoom.

Clinical Trials (3)

Relevant trials from ClinicalTrials.gov

Active

0

Completed

3

Total Enrollment

174

By Phase

PHASE2: 1 · PHASE4: 1 · Unknown: 1

Clinical Efficacy of Diazepam After Whiplash Completed

PHASE4 NCT05041985 n=89

Whiplash Injuries, Whiplash Injury of Cervical Spine

Interventions: Diazepam Tablets

Sponsor: Edin Mešanović | Started: 2020-01-01

Study of Diazepam Buccal Film Administered in the Interictal and in the Ictal-Periictal States to Adults With Epilepsy Completed

PHASE2 NCT03179891 n=35

Epilepsy

Interventions: Diazepam Buccal Film 12.5 mg

Sponsor: Aquestive Therapeutics | Started: 2017-05-25

Fixed-schedule Benzodiazepine Dosing vs Based on a CIWA-Ar Alcohol Protocol in Alcohol Detoxification. Completed

Unknown NCT04777552 n=50

Alcoholdependence, CIWA-R, Benzodiazepines

Interventions: diazepam (or equivalence if other benzod

Sponsor: Universitair Ziekenhuis Brussel | Started: 2015-10

Linked Hypotheses (10)

Closed-loop optogenetic targeting PV interneurons to restore theta-gamma coupling and prevent amyloi0.952

Optogenetic restoration of hippocampal gamma oscillations via selective PV interneuron activation us0.865

Closed-loop focused ultrasound targeting EC-II PV interneurons to restore theta-gamma coupling and p0.863

Closed-loop tACS targeting EC-II parvalbumin interneurons to restore gamma rhythmogenesis and block 0.849

Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via glymphatic0.827

Closed-loop transcranial focused ultrasound targeting CA1 PV interneurons with real-time gamma feedb0.797

Prefrontal sensory gating circuit restoration via PV interneuron enhancement0.775

Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via direct PV 0.773

Closed-loop tACS targeting EC-II PV interneurons to suppress burst firing and block tau propagation 0.764

Closed-loop focused ultrasound targeting CA1 PV interneurons to restore theta-gamma coupling and blo0.716

Linked Experiments (1)

Closed-loop tFUS Enhances Glymphatic Clearance and Restores CA1 PV Interneuron Gamma in APP/PS1 Mice0.765

Scoring Dimensions

Knowledge Graph (20)

associated with (8)

CASP3→PVALBPVALB→TNFPVALB→APPPVALB→BDNFPVALB→DLG4

▸ Show 3 more

APP→PVALBTNF→PVALBDLG4→PVALB

co discussed (5)

PVALB→SIRT3PVALB→PDGFRBPVALB→SREBF2PVALB→GFAPPVALB→SLC16A1

expressed in (1)

PVALB→Amygdala

interacts with (4)

FKBP5→PVALBPVALB→NR3C1NR3C1→PVALBPVALB→FKBP5

involved in (1)

PVALB→Thalamo-Amygdala Signaling

participates in (1)

PVALB→Prefrontal inhibitory circuits

Debate History (1)

Should PVALB (Parvalbumin) be prioritized as a therapeutic target for neurodegen2026-04-26