G3BP1

Ras GTPase-activating protein-binding protein 1

Score: 0.636 Price: $0.64 Medium Druggability Status: active Wiki: G3BP1

🧠 Neurodegeneration

HYPOTHESES

4

PAPERS

87

KG EDGES

559

DEBATES

1

3D Protein Structure

🧬 G3BP1 — PDB 4FCJ Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.47

Clinical Stage

Phase II

Target Class

Signaling Protein

Safety

0.50

Druggability Analysis

Drug Development0.30

Structural Tractability0.85

Target Class0.50

Safety Profile0.50

Key Metrics

PDB Structures:

18

Known Drugs:

1

Approved:

0

In Clinical Trials:

0

Drug Pipeline (1 compounds)

1 Preclinical

Druggability Rationale: G3BP1 presents medium druggability (0.55) due to available structural data (18 PDB structures, 1.62 Å resolution) and defined protein domains, but is challenged by its primary role as an RNA-binding protein and stress granule scaffolding component, which favors protein-protein interactions over traditional small-molecule binding. The investigational status of resveratrol demonstrates early-stage tractability, though off-target effects highlight the difficulty in achieving selective G3BP1 inhibition via conventional approaches.

Mechanism: G3BP1 inhibitors would prevent stress granule assembly and stabilization by disrupting the interaction between G3BP1 and its binding partners, potentially reducing pathological aggregation of TDP-43 and FUS proteins. This mechanism could alleviate neurodegeneration in conditions characterized by aberrant stress granule formation and RNA metabolism dysfunction.

Drug Pipeline (1 compounds)

1 Preclinical

Known Drugs:

Resveratrol (investigational) — Stress granule modulator, neuroprotection (off-target)

Structural Data:

PDB (18) ✓AlphaFold ✓Cryo-EM ✓

3Q90 4FCJ 4FCM 4IIA 6TA7+13 more

UniProt: A0A7I2V3C4

🧬 3D Protein Structure

🧬 G3BP1 — PDB 4FCJ Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

G3BP1 selectivity is complicated by its structural homology to G3BP2 and other RNA-binding proteins, as well as its multiple functional domains (NTF2-like domain, RRM, acidic regions) that may interact with numerous cellular partners. Off-target engagement with stress response pathways and RNA metabolism machinery presents a significant risk, requiring careful structural optimization to achieve isoform selectivity without disrupting essential cellular stress responses.

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 (7)

Relevant trials from ClinicalTrials.gov

Active

2

Completed

4

Total Enrollment

274

By Phase

NA: 7

Possible Action of Resveratrol in Improving the Outcomes of IVF/ICSI in Couples With Unexplained Infertility Recruiting

NA NCT06481696 n=90

Unexplained Infertility

Interventions: Resveratrol-based multivitamin supplemen, Folic acid, IVF/ICSI

Sponsor: Andros Day Surgery Clinic | Started: 2024-06-01

Effect of Supplement on Appetite and GLP-1 Not Yet Recruiting

NA NCT06790771 n=25

Hunger

Interventions: High Dose Supplement, Low Dose Supplement, Placebo

Sponsor: Texas Christian University | Started: 2025-01-15

Resveratrol and First-degree Relatives of Type 2 Diabetic Patients Completed

NA NCT02129595 n=15

Pre-diabetes

Interventions: placebo, resveratrol

Sponsor: Maastricht University Medical Center | Started: 2014-04

Effect of Resvida, a Comparison With Calorie Restriction Regimen Completed

NA NCT00823381 n=58

Obesity, Metabolic Syndrome, Diabetes

Interventions: resveratrol, placebo, Calorie Restriction

Sponsor: Washington University School of Medicine | Started: 2009-01

Grape Polyphenol Kinetics in Humans Completed

NA NCT01751750 n=16

Healthy Volunteers

Interventions: Grape

Sponsor: Janet Novotny | Started: 2011-09

Long-term Investigation of Resveratrol on Fat Metabolism in Obese Men With Nonalcoholic Fatty Liver Disease Completed

NA NCT01446276 n=26

Obesity, Nonalcoholic Fatty Liver Disease

Interventions: Resveratrol, Placebo

Sponsor: University of Aarhus | Started: 2011-11

The Effects of Resveratrol Supplementation on Measurements of Health and Human Performance Unknown

NA NCT01244360 n=44

Inflammation

Interventions: resveratrol, Placebo Comparator: Sugar Pill

Sponsor: Marywood University | Started: 2010-11

Linked Hypotheses (10)

Ubiquitin-Mediated Liquid-to-Solid Transition Prevention0.730

Phase-Separated Organelle Targeting0.729

Autophagic Receptor Sequestration via K63-Ub 'Signalone' Recognition0.720

Stress Granule Phase Separation Modulators0.720

RNA Granule Nucleation Site Modulation0.662

G3BP1 NTF2L Domain-Mediated mRNP Scaffold Creates Core Exclusion Zone for Autophagy Receptors0.633

Steric Occlusion of G3BP1 Oligomerization Interface0.630

ALS-Associated G3BP1 Mutations Shift Phase Separation Equilibrium Toward Aberrant Condensate Stabili0.610

Displacement of G3BP1 RGG Box from Target RNA via Ubiquitin-Mediated Allostery0.600

G3BP1 Haploinsufficiency Reveals a Therapeutic Window for SG-Targeting Interventions0.590

Linked Experiments (4)

TRIM21-mediated K63-linked ubiquitination of G3BP10.950

G3BP1-mediated stress granule assembly via liquid-liquid phase separation0.900

G3BP1 intrinsically disordered region analysis and phosphorylation effects0.850

G3BP1-binding factor cooperativity in stress granule network regulation0.800

Scoring Dimensions

Knowledge Graph (20)

associated with (1)

G3BP1→neurodegeneration

co discussed (18)

TGM2→G3BP1PRMT1→G3BP1PARP1→G3BP1HSPA1A→G3BP1G3BP1→SRPK1

▸ Show 13 more

TARDBP→G3BP1BMAL1→G3BP1CLOCK→G3BP1PLIN2→G3BP1DGAT1→G3BP1CNO→G3BP1TUBB3→G3BP1PIEZO1→G3BP1GABRA1→G3BP1SETX→G3BP1HNRNPA2B1→G3BP1NPM1→G3BP1SYNCRIP→G3BP1

interacts with (1)

Debate History (1)

Should G3BP1 (Ras GTPase-activating protein-binding protein 1) be prioritized as2026-04-21