AQP1

Aquaporin-1

Score: 0.553 Price: $0.55 Low Druggability Status: active Wiki: AQP1
🧠 Neurodegeneration
HYPOTHESES
1
PAPERS
26
KG EDGES
125
DEBATES
1

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:
3
Known Drugs:
1
Approved:
1
In Clinical Trials:
0
Drug Pipeline (1 compounds)
1 Approved
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 ✓
6POJ7W7R7W7S
UniProt: A0A024RA31

🧬 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.

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 (6)

Relevant trials from ClinicalTrials.gov

Active
1
Completed
3
Total Enrollment
449
By Phase
EARLY_PHASE1: 1 · PHASE1: 1 · PHASE3: 1 · PHASE4: 3
Stent Implantation Versus Medical Therapy for Idiopathic IntracraniaL Hypertension (SIMPLE) Recruiting
PHASE3 NCT05707442 n=74
Idiopathic Intracranial Hypotension, Venous Sinus Stenosis
Interventions: Stent Implantation, Acetazolamide-based medical therapy, Weight loss
Sponsor: Beijing Tiantan Hospital | Started: 2023-02-16
Effect of Acetazolamide on Cognition in Patients With Respiratory Disease at Altitude Completed
PHASE4 NCT03165890 n=78
Chronic Obstructive Pulmonary Disease (C
Interventions: ACETAZOLAMIDE oral capsule, Placebo oral capsule
Sponsor: University of Zurich | Started: 2017-05-24
Optimization Strategy for the Prevention of AMS by RIPC Combined With Acetazolamide Completed
PHASE4 NCT05023941 n=252
Acute Mountain Sickness
Interventions: Acetazolamide, Doctormate® (twice daily for 6 days), Doctormate® (forth daily for 3 days)
Sponsor: Ji Xunming,MD,PhD | Started: 2021-12-01
Impact of Acetazolamide in Reducing Referred Postoperative Pain Completed
PHASE1 NCT04470843 n=33
Prostate Cancer, Men
Interventions: Acetazolamide, Placebo
Sponsor: Medical College of Wisconsin | Started: 2018-08-22
A Noninvasive Arterial Input Estimation Method for O-15 PET and Integrated PET/MR Scanning Withdrawn
EARLY_PHASE1 NCT03806751
Validation of a New Noninvasive Method t
Interventions: [O-15]Water, Acetazolamide
Sponsor: University of Alabama at Birmingham | Started: 2025-02-01
Effect of Acetazolamide on Central Sleep Apnea Related to Opium Consumption Unknown
PHASE4 NCT02371473 n=12
Central Sleep Apnea, Secondary
Interventions: Acetazolamide-placebo, Placebo-acetazolamide
Sponsor: Shahid Beheshti University of Medical Sciences | Started: 2014-11

Linked Hypotheses (1)

Osmotic Gradient Restoration via Selective AQP1 Enhancement in Choroid Plexus0.680

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Portfolio 0.65 (25%) Druggability 0.39 (20%) Evidence 0.54 (20%) Safety 0.50 (15%) Competitive 0.40 (10%) Connectivity 0.90 (10%) 0.553 composite

Knowledge Graph (20)

associated with (3)

AQP1neurodegenerationAQP4AQP1AQP1AQP4

co discussed (9)

AQP1KCNK2AQP1GJA1AQP1HCRTR2AQP1LOXL1-4AQP1HCRTR1
▸ Show 4 more
AQP1AQP4AQP1LOXAQP1SDC1AQP1PDGFRB

expressed in (2)

AQP4AQP1AQP1AQP4

inhibits (3)

HDAC4AQP1MEF2AAQP1AQP1HDAC4

regulates (3)

CFTRAQP1GAT1AQP1AQP1CFTR

Debate History (1)

Should AQP1 (Aquaporin-1) be prioritized as a therapeutic target for neurodegene2026-04-22