FOXO1

Forkhead box protein O1

Score: 0.579 Price: $0.58 Medium Druggability Status: active Wiki: FOXO1

🧠 Neurodegeneration

HYPOTHESES

1

PAPERS

28

KG EDGES

698

DEBATES

1

3D Protein Structure

🧬 FOXO1 — PDB 3CO6 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.55

Clinical Stage

Phase I

Target Class

Transcription Factor

Safety

0.30

Druggability Analysis

Drug Development0.15

Structural Tractability0.70

Target Class0.50

Safety Profile0.30

Key Metrics

PDB Structures:

7

Known Drugs:

3

Approved:

0

In Clinical Trials:

0

Drug Pipeline (3 compounds)

2 Preclinical

Druggability Rationale: FOXO1 presents medium druggability (0.55 score) due to its transcription factor nature, which traditionally poses challenges for small molecule modulation; however, the availability of 7 crystal structures at high resolution (1.6 Å) and successful tool compounds (AS1842856) demonstrate feasibility of targeting protein-DNA and cofactor interactions. The existing preclinical pipeline for metabolic and neurodegenerative indications validates the therapeutic potential despite the inherent difficulty of modulating transcriptional activity.

Mechanism: Small molecule modulation of protein-DNA interactions or cofactor binding

Drug Pipeline (3 compounds)

2 Preclinical

Known Drugs:

AS1842856 (tool_compound) — research tool for FOXO1 inhibition

FOXO1 siRNA (preclinical) — metabolic disorders

Compound 1 (FOXO1-targeting small molecule) (preclinical) — diabetes

Structural Data:

PDB (7) ✓AlphaFold ✓Cryo-EM —

3CO6 3CO7 3COA 4LG0 5DUI+2 more

UniProt: Q12778

🧬 3D Protein Structure

🧬 FOXO1 — PDB 3CO6 Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

FOXO1 selectivity is complicated by its membership in the FOXO family (FOXO1/3/4/6), which share highly homologous DNA-binding domains and overlapping cellular functions; achieving isoform selectivity will likely require targeting divergent cofactor-binding regions or protein-protein interaction interfaces rather than the conserved forkhead domain itself.

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 (8)

Relevant trials from ClinicalTrials.gov

Active

1

Completed

7

Total Enrollment

860

By Phase

NA: 5 · PHASE1: 1 · PHASE2: 1 · Unknown: 1

Anger Control Training for Youth With Tourette Syndrome Completed

NA NCT00486551 n=26

Tourette Syndrome, Chronic Tic Disorder, Oppositional Defiant Disorder

Interventions: Anger control training

Sponsor: Yale University | Started: 2001-08

Adaptive vs. Continuous Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease Recruiting

NA NCT06909045 n=130

Deep Brain Stimulation, Parkinson Disease

Interventions: Adaptive DBS, Continue DBS

Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC | Started: 2026-01-27

Expiratory Muscle Training in Patients With Parkinson's Disease Completed

PHASE1 NCT00843739 n=90

Parkinson's Disease

Interventions: EMST - Active Treatment, sham EMST

Sponsor: University of Florida | Started: 2004-01

Study of the Follow-up of Stroke Treated With Anticoagulants Completed

Unknown NCT03292575 n=441

Stroke

Interventions: Anticoagulants

Sponsor: Centre Hospitalier Universitaire Dijon | Started: 2016-01

Early Detection and Prevention of Mild Cognitive Impairment Due to Cerebrovascular Disease Completed

NA NCT01924312 n=80

Cerebrovascular Disease, Mild Cognitive Impairment

Interventions: Heart Health Intervention

Sponsor: Gregory Jicha, 323-5550 | Started: 2013-05

Effects of Modern Board Games on Well Being in Older Adults Completed

NA NCT06306365 n=35

Executive Functions

Interventions: Modern board game-based learning

Sponsor: European University Miguel de Cervantes | Started: 2024-02-07

Treatment of Alzheimer's and Dementia With the Metabolism, Infections, Nutrition, Drug Elimination (MIND) Protocol Completed

NA NCT02260167 n=25

Alzheimer's Disease, Dementia

Interventions: A mix of natural treatments and medicati

Sponsor: Practitioners Alliance Network | Started: 2014-09

A Phase 2 Study to Evaluate Safety of Long-term AL001 Dosing in Frontotemporal Dementia (FTD) Patients (INFRONT-2) Completed

PHASE2 NCT03987295 n=33

Frontotemporal Dementia

Interventions: AL001

Sponsor: Alector Inc. | Started: 2019-09-27

Linked Hypotheses (1)

Transcriptional Autophagy-Lysosome Coupling0.757

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

activates (2)

FOXO1→CCL4SOD2→FOXO1

associated with (2)

EHMT2→FOXO1FOXO1→BCL2

co discussed (6)

STX17→FOXO1CHMP2B→FOXO1LAMP1→FOXO1MCOLN1→FOXO1FOXO1→IGF2R

▸ Show 1 more

inhibits (1)

interacts with (5)

PPARA→FOXO1ULK1→FOXO1STX17→FOXO1SQSTM1→FOXO1NOS3→FOXO1

therapeutic target (4)

PPARGC1A→FOXO1SIRT3→FOXO1PRKAA1→FOXO1CREBBP→FOXO1

Debate History (1)

Should FOXO1 (Forkhead box protein O1) be prioritized as a therapeutic target fo2026-04-21