AQP1

Aquaporin-1

Score: 0.625 Price: $0.62 Low Druggability Status: active Wiki: AQP1

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

125

DEBATES

3D Protein Structure

🧬 AQP1 — PDB 1J4N Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.39

Clinical Stage

Approved

Target Class

Ion Channel

Safety

0.50

Druggability Analysis

Drug Development0.75

Structural Tractability0.70

Target Class0.85

Safety Profile0.50

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (1 compounds)

1 Approved

Therapeutic Areas:

Cerebral edema Acute ischemic stroke Traumatic brain injury Neurotoxic brain swelling Glaucoma (aqueous humor regulation) Neurodegenerative diseases with edema component

Druggability Rationale: AQP1 represents a promising druggable target for neurodegeneration due to its role in water transport and potential involvement in neuroinflammatory processes. The availability of high-resolution structural data and existing inhibition strategies like acetazolamide suggest potential for targeted therapeutic intervention, with the channel's precise structural characterization enabling rational drug design approaches. The AlphaFold prediction and multiple PDB structures provide a robust structural framework for understanding potential small molecule binding mechanisms.

Mechanism: AQP1 functions as a water channel protein facilitating transmembrane water flux, with emerging evidence suggesting its involvement in neuroinflammatory processes and potential contribution to neuronal cell volume regulation and edema formation in neurodegenerative conditions. In the context of neurodegeneration, AQP1 may modulate neuronal and glial cell responses to oxidative stress, inflammation, and cellular metabolic perturbations, making it a potential strategic target for therapeutic intervention.

Drug Pipeline (1 compounds)

1 Approved

Known Drugs:

Acetazolamide (approved) — Glaucoma, epilepsy, altitude sickness

Structural Data:

PDB (3) ✓AlphaFold ✓Cryo-EM ✓

6POJ 7W7R 7W7S

UniProt: A0A024RA31

Binding Pocket Analysis:

The water-conducting pore features a narrow selectivity filter (~3 Å diameter) with conserved asparagine-proline-alanine (NPA) motifs that coordinate water molecules; modulators likely bind at the pore entrance or allosteric sites flanking the central channel. High-resolution structural data (PDB: 6POJ, 7W7R, 7W7S) enables structure-based design targeting the extracellular or intracellular vestibules where gating can be modulated.

🧬 3D Protein Structure

🧬 AQP1 — PDB 1J4N Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

AQP1 selectivity is challenging due to the high sequence homology across the aquaporin family (AQP0-AQP12), which could lead to off-target modulation of other water channels. However, structural divergence in the selectivity filter and C-terminus regions provides opportunities for isoform-selective inhibitors to minimize effects on aquaporins involved in other physiological processes.