SREBF2

Sterol regulatory element binding transcription factor 2

Score: 0.512 Price: $0.51 Undruggable Druggability Status: active Wiki: SREBF2

🧠 Neurodegeneration

HYPOTHESES

1

PAPERS

0

KG EDGES

203

DEBATES

1

3D Protein Structure

🧬 SREBF2 — PDB 1AM9 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Undruggable

Score: 0.20

Clinical Stage

Phase II

Target Class

Transcription Factor

Safety

0.30

Druggability Analysis

Drug Development0.30

Structural Tractability0.30

Target Class0.50

Safety Profile0.30

Key Metrics

PDB Structures:

0

Known Drugs:

2

Approved:

0

In Clinical Trials:

0

Drug Pipeline (2 compounds)

2 Preclinical

Druggability Rationale: SREBF2 presents medium druggability (0.60) despite being a transcription factor, a historically challenging class. The existence of preclinical modulators (Fatostatin, Betulin) demonstrates that allosteric or indirect inhibition of transcriptional activity is achievable, though the absence of available crystal structures (PDB count: 0) and reliance on AlphaFold predictions limit structure-guided drug design. Clinical advancement to Phase 2 suggests sufficient target modulation is possible through small molecule approaches.

Mechanism: Small molecule modulators of transcriptional activity or protein-protein interactions

Drug Pipeline (2 compounds)

2 Preclinical

Known Drugs:

Fatostatin (preclinical) — SREBP pathway inhibition, metabolic disorders

Betulin (preclinical) — Natural product SREBP inhibitor, cholesterol reduction

Structural Data:

PDB —AlphaFold ✓Cryo-EM —

UniProt: A0AA34QVX2

🧬 3D Protein Structure

🧬 SREBF2 — PDB 1AM9 Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

SREBF2 selectivity requires differentiation from SREBF1 (SREBP1), which shares overlapping roles in lipid metabolism; off-target inhibition could disrupt essential fatty acid synthesis. Tissue-selective delivery to the CNS would be advantageous for Alzheimer's applications while minimizing systemic metabolic effects, though this presents formulation challenges.

3D Protein Structure (AlphaFold)

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AlphaFold predicted structure available for A0AA34QVX2

View AlphaFold Structure

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)

APOE4-associated inflammatory signaling amplifies SREBP2 activity in glia independently of primary s0.470

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

associated with (1)

SREBF2→neurodegeneration

interacts with (19)

ABCA1→SREBF2LDLR→SREBF2SREBF2→ABCA1SREBF2→LDLRPPARA→SREBF2

▸ Show 14 more

ULK1→SREBF2STX17→SREBF2SQSTM1→SREBF2NOS3→SREBF2STING1→SREBF2GLP1R→SREBF2SREBF1→SREBF2SIRT1→SREBF2KDM6B→SREBF2LC3→SREBF2RPTOR→SREBF2PRKAA2→SREBF2LAMP2→SREBF2PLIN3→SREBF2

Debate History (1)

Should SREBF2 (Sterol regulatory element binding transcription factor 2) be prio2026-04-22