CLOCK

Circadian Locomotor Output Cycles Kaput

Score: 0.537 Price: $0.54 Low Druggability Status: active Wiki: CLOCK

🧠 Neurodegeneration

HYPOTHESES

14

PAPERS

81

KG EDGES

908

DEBATES

0

3D Protein Structure

🧬 CLOCK — PDB 4F3L Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.35

Clinical Stage

Approved

Target Class

Transcription Factor

Safety

0.40

Druggability Analysis

Drug Development0.60

Structural Tractability0.85

Target Class0.50

Safety Profile0.40

Key Metrics

PDB Structures:

10

Known Drugs:

1

Approved:

0

In Clinical Trials:

0

Drug Pipeline (1 compounds)

1 Preclinical

Therapeutic Areas:

Oncology Immunology Rare Disease

Druggability Rationale: The CLOCK transcription factor presents challenging druggability due to its complex protein-protein interaction dynamics and nuclear localization, with limited small molecule modulators currently available. While preclinical compounds like CLK8 suggest potential intervention strategies, the target's intricate transcriptional regulation mechanism and low structural tractability significantly constrain conventional drug discovery approaches. The emerging research on circadian rhythm modulation in neurodegenerative contexts indicates promising translational potential, but substantial medicinal chemistry efforts are required to develop selective and bioavailable CLOCK-targeted therapeutics.

Mechanism: Modulation of circadian transcriptional activity through protein-protein interaction disruption

Drug Pipeline (1 compounds)

1 Preclinical

Known Drugs:

CLK8 (preclinical) — Circadian rhythm disorders

Structural Data:

PDB (10) ✓AlphaFold ✓Cryo-EM —

4F3L 4H10 5VJI 5VJX 6QPJ+5 more

UniProt: O15516

Binding Pocket Analysis:

DNA-binding domain, dimerization interface

🧬 3D Protein Structure

🧬 CLOCK — PDB 4F3L Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

Selectivity among transcription factor family members is challenging but critical, as broad transcriptional disruption can cause widespread toxicity.

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

3

Completed

6

Total Enrollment

3,265

By Phase

NA: 6 · PHASE3: 1 · Unknown: 3

Transcranial Pulse Stimulation (TPS) for Alzheimer's Disease (AD) Completed

NA NCT04333329 n=15

Alzheimer Disease

Interventions: NEUROLITH

Sponsor: Storz Medical AG

Non-invasive Diagnosis of Parkinson's Disease Not Yet Recruiting

Unknown NCT07201610 n=60

Parkinsons Disease (PD)

Sponsor: Blekinge Institute of Technology

Differences Between Patients With Vascular Parkinsonism and Parkinson's Disease Completed

Unknown NCT04308135 n=104

Vascular Parkinsonism, Parkinson's Disease

Interventions: Neuro-radiological tools:, cognitive tests, lab investigations

Sponsor: Ain Shams University

Study of a Strategy to Prevent Oversedation in Intensive Care Patients Under Mechanical Ventilation Completed

NA NCT01617265 n=1180

ICU Patients Requiring Invasive Mechanic

Interventions: Clinical Procedure to Prevent Oversedati, Usual sedation practice

Sponsor: French Society for Intensive Care

Optimized Acute Care for Geriatric Patients Using an Intersectoral Telemedical Cooperation Network - Around the Clock Completed

NA NCT04879537 n=1600

Emergencies

Interventions: Telemedical support

Sponsor: RWTH Aachen University

Linus Health CDS Retrospective Validation Study Unknown

Unknown NCT05900310 n=40

Cognitive Impairment, Motor Disorders, Dementia

Interventions: Core Cognitive Evaluation (CCE)

Sponsor: Linus Health, Inc.

Comparison of the Ultrasound-guided Paravertebral Nerve Block With Liposomal Bupivacaine Versus Ropivacaine for Post-Sur Not Yet Recruiting

PHASE3 NCT06405724 n=84

Analgesia

Interventions: Liposomal bupivacaine, Ropivacaine

Sponsor: Feng Gao

Age Dependents Benefits of Virtual Reality Rehabilitation Completed

NA NCT05922046 n=16

Parkinson Disease

Interventions: Leap Motion Controller on flat display

Sponsor: Federal University of Health Science of Porto Alegre

Linked Hypotheses (2)

Circadian Clock-Autophagy Synchronization0.547

Temporal Decoupling via Circadian Clock Reset0.516

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

associated with (1)

CLOCK → neurodegeneration

co discussed (18)

CLOCK → GPR37

CLOCK → CMKLR1

CLOCK → ALOX12

CLOCK → ALOX5

...and 13 more

interacts with (1)

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