GFAP

Glial fibrillary acidic protein

Score: 0.408 Price: $0.41 Medium Druggability Status: active Wiki: GFAP

HYPOTHESES

1

PAPERS

24

KG EDGES

1343

DEBATES

1

3D Protein Structure

🧬 GFAP — PDB 3IFS Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.52

Clinical Stage

Phase II

Target Class

Structural Protein

Safety

0.90

Druggability Analysis

Drug Development0.30

Structural Tractability0.70

Target Class0.50

Safety Profile0.90

Key Metrics

PDB Structures:

3

Known Drugs:

3

Approved:

0

In Clinical Trials:

0

Drug Pipeline (3 compounds)

Druggability Rationale: GFAP is a structural cytoskeletal protein with inherently low druggability (0.25 score) and lacks direct binding pockets suitable for small-molecule inhibition. Therapeutic intervention requires indirect modulation through upstream inflammatory pathways (NF-κB, JAK-STAT) rather than direct GFAP targeting, making it more suitable as a biomarker readout for drug efficacy than as a primary drug target.

Mechanism: Biomarker readout — GFAP levels reflect astrocyte reactivity; modulating upstream pathways (e.g., NF-κB, JAK-STAT) reduces GFAP expression

Drug Pipeline (3 compounds)

Known Drugs:

UCB0599 (Minzasolmin) (Phase II)

Lecanemab (Approved)

Donanemab (Approved)

Structural Data:

PDB (3) ✓AlphaFold ✓Cryo-EM —

UniProt: P14136

Selectivity & Safety Considerations

GFAP selectivity is not a traditional concern since it is astrocyte-specific; however, peripheral astrocyte activation versus CNS astrocytes presents a challenge for biomarker interpretation. Off-target risk is minimal for GFAP-targeting agents, but upstream pathway modulators (NF-κB, JAK-STAT inhibitors) will have broad systemic effects across immune and other cell types.

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

8

Completed

0

Total Enrollment

12,975

By Phase

NA: 1 · PHASE2: 1 · PHASE3: 1 · PHASE4: 2 · Unknown: 3

Prospective Cohort Study of Patients With Early Alzheimer's Disease Treated With Lecanemab Recruiting

Unknown NCT06741553 n=120

Alzheimer Disease, Mild Cognitive Impairment (MCI)

Interventions: Lecanemab 10 mg/kg

Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang Uni | Started: 2024-06-28

A Post Marketing Study in Participants With Early Alzheimer's Disease Treated With Lecanemab Recruiting

Unknown NCT06322667 n=5000

Alzheimer's Disease

Interventions: No Intervention

Sponsor: Eisai Co., Ltd. | Started: 2024-02-14

A Real-World Comparative Study of Donanemab (LY3002813) Plus Usual Care Versus Usual Care Alone in US Participants With Recruiting

Unknown NCT06566170 n=6250

Alzheimer Disease

Interventions: Donanemab, Usual Care

Sponsor: Eli Lilly and Company | Started: 2024-10-07

Amyloid Lowering for Alzheimer's in Down's With Donanemab Investigation Not Yet Recruiting

PHASE4 NCT06911944 n=60

Down Syndrome (DS), Down Syndrome (Trisomy 21), Alzheimer Disease

Interventions: Donanemab, Placebo

Sponsor: Michael Rafii, MD, PhD | Started: 2026-08-01

A Study of Donanemab, RG6289, or the Combination of Donanemab and RG6289 in Presenilin 1 (PSEN1) E280A Mutation Carriers Not Yet Recruiting

PHASE2 NCT06996730 n=240

Autosomal Dominant Alzheimers Disease, Early Onset Alzheimer Disease, Alzheimers Disease

Interventions: Donanemab, RG6289, Donanemab placebo

Sponsor: Banner Health | Started: 2026-01-15

Making Antibody Treatments More Effective in Early Alzheimer's Disease Using 3Tesla Magnetica Resonance Not Yet Recruiting

NA NCT07456462 n=50

Alzheimer Dementia (AD), Mild Cognitive Impairment (MCI)

Interventions: MRI assessment and blood sample collecti

Sponsor: IRCCS San Raffaele | Started: 2026-05-01

12-Month Real-World Safety & Efficacy of Lecanemab in Early Alzheimer's Disease Active Not Recruiting

PHASE4 NCT07034222 n=80

Alzheimer's Disease(AD)

Interventions: Administer Leqemi 10 mg/kg, every two we

Sponsor: Ruijin Hospital | Started: 2024-02-01

A Study of Different Donanemab (LY3002813) Dosing Regimens in Adults With Early Alzheimer's Disease (TRAILBLAZER-ALZ 6) Active Not Recruiting

PHASE3 NCT05738486 n=1175

Alzheimer's Disease, Dementia, Brain Diseases

Interventions: Donanemab, Placebo, Dexamethasone

Sponsor: Eli Lilly and Company | Started: 2023-02-28

Linked Hypotheses (3)

GFAP-Positive Reactive Astrocyte Subtype Delineation0.754

Heterogeneous astrocyte activation states differentially impact neuronal survival across AD progress0.640

Age-related neuroinflammation mimics early Alzheimer's disease pathology0.362

Linked Experiments (1)

Blood Biomarker vs Tau PET for Treatment Monitoring0.400

Scoring Dimensions

Knowledge Graph (20)

activates (2)

VANADIUM→GFAPTMT→GFAP

associated with (3)

GFAP→neuroinflammationGFAP→ASTROGLIAL_ACTIVATIONGFAP→ALEXANDER_DISEASE

expressed in (2)

S100A8→GFAPGFAP→CD68

inhibits (5)

CD47→GFAPGFAP→MMP9GFAP→TNFGFAP→TLR4GFAP→MMP2

interacts with (1)

PHENYTOIN→GFAP

participates in (2)

GFAP→CYTOSKELETONGFAP→INTERMEDIATE_FILAMENTS

regulates (5)

JAK2→GFAPSTAT3→GFAPGFAP→NOTCH_SIGNALINGGFAP→DLK2GFAP→SOX2

Debate History (1)

Should GFAP (Glial fibrillary acidic protein) be prioritized as a therapeutic ta2026-04-22