CNO

Cappuccino

Score: 0.433 Price: $0.43 Low Druggability Status: active Wiki: CNO

🧠 Neurodegeneration

HYPOTHESES

1

PAPERS

32

KG EDGES

62

DEBATES

1

3D Protein Structure

🧬 CNO — PDB 7MFW Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.30

Clinical Stage

Phase III

Target Class

Other

Safety

0.30

Druggability Analysis

Drug Development0.45

Structural Tractability0.70

Target Class0.50

Safety Profile0.30

Key Metrics

PDB Structures:

1

Known Drugs:

1

Approved:

0

In Clinical Trials:

0

Drug Pipeline (1 compounds)

Druggability Rationale: Clozapine-N-oxide (CNO) demonstrates limited druggability for neurodegeneration due to its lack of established direct therapeutic mechanisms and minimal clinical validation in neurodegenerative contexts. While CNO has been primarily utilized as a research tool, particularly in chemogenetic studies, its potential as a direct neurodegeneration therapeutic remains speculative, with current clinical trials focusing on psychosis-related indications rather than neurodegenerative disease modification. The structural complexity and absence of clear target-specific binding profiles suggest CNO requires significant medicinal chemistry optimization to emerge as a promising neurodegeneration drug candidate.

Mechanism: No established druggable mechanisms

Drug Pipeline (1 compounds)

Known Drugs:

Clozapine-N-oxide (research) — DREADD ligand, chemogenetic tool compound

Structural Data:

PDB (1) ✓AlphaFold ✓Cryo-EM —

UniProt: Q9NUP1

🔮 Predicted Protein Structure (AlphaFold)

🔮 CNO — AlphaFold Q9NUP1 Click to expand interactive 3D viewer

AI-predicted structure from AlphaFold EBI | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Selectivity & Safety Considerations

As a unique intracellular trafficking protein with limited homologs, CNO offers potential for high selectivity and low off-target risk. However, selectivity challenges may arise if targeting protein-protein interaction interfaces critical to melanosome trafficking complexes, requiring careful validation of effects on related trafficking machinery.

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 (10)

Relevant trials from ClinicalTrials.gov

Active

6

Completed

4

Total Enrollment

17,767

By Phase

PHASE2: 4 · PHASE3: 6

A Study to Evaluate KarXT as a Treatment for Psychosis Associated With Alzheimer's Disease (ADEPT-4) Recruiting

PHASE3 NCT06585787 n=406

Alzheimer Disease

Interventions: KarXT, Placebo

Sponsor: Karuna Therapeutics, Inc., a Bristol Myers Squibb company

Assessment of Acute Psychomotor Agitation Measures Associated With Schizophrenia and Bipolar Disorder Active Not Recruiting

PHASE2 NCT07116694 n=30

Bipolar I Disorder, Bipolar II Disorder, Schizophrenia

Interventions: BXCL501 Sublingual Film

Sponsor: BioXcel Therapeutics Inc

Open-Label Extension Study to Assess the Long-Term Safety and Tolerability of KarXT in Subjects With Psychosis Associate Recruiting

PHASE3 NCT05980949 n=800

Psychosis Associated With Alzheimer'

Interventions: KarXT

Sponsor: Karuna Therapeutics, Inc., a Bristol Myers Squibb company

Study to Evaluate the Efficacy, Safety, and Tolerability of BMS-986368, for the Treatment of Agitation in Participants W Recruiting

PHASE2 NCT06808984 n=120

Agitation, Alzheimer Disease

Interventions: BMS-986368, Placebo

Sponsor: Celgene

Safety and Cognitive Function Study of EVP-6124 in Patients With Mild to Moderate Alzheimer's Disease Completed

PHASE2 NCT01073228 n=409

Alzheimer's Disease, Central Nervous System Diseases, Cognition

Interventions: EVP-6124, Placebo

Sponsor: FORUM Pharmaceuticals Inc

Efficacy and Safety of Oxycodone/Naloxone Controlled-release Tablets (OXN) Compared to Placebo in Opioid-experienced Sub Completed

PHASE3 NCT01358526 n=1095

Low Back Pain

Interventions: Oxycodone/Naloxone Controlled-release, Placebo

Sponsor: Purdue Pharma LP

A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients. Active Not Recruiting

PHASE3 NCT05739383 n=14078

Primary Prevention of Atherosclerotic Ca

Interventions: Inclisiran sodium 300 mg (equivalent to , Placebo in 1.5ml

Sponsor: Novartis Pharmaceuticals

Fentanyl Buccal Tablets Versus Immediate Release Oxycodone for Breakthrough Pain in Patients With Chronic Pain Completed

PHASE3 NCT00813488 n=213

Chronic Pain

Interventions: Fentanyl Buccal Tablet, Immediate release oxycodone

Sponsor: Cephalon

Linked Hypotheses (1)

Synthetic Biology Rewiring via Orthogonal Receptors0.645

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

activates (1)

associated with (1)

CNO→neurodegeneration

co discussed (12)

BMAL1→CNOCNO→TUBB3CNO→CLOCKCNO→PLIN2CNO→PIEZO1

▸ Show 7 more

CNO→GABRA1CNO→G3BP1PLIN2→CNOG3BP1→CNOTUBB3→CNOCNO→BMAL1CLOCK→CNO

implicated in (1)

CNO→neurodegeneration

inhibits (1)

participates in (1)

CNO→Synthetic biology / chemogenetics

regulates (1)

CNO→Dopamine Signaling

targets (1)

h-e3506e5a→CNO

therapeutic target (1)

Debate History (1)

Should CNO (Cappuccino) be prioritized as a therapeutic target for neurodegenera2026-04-22