SciDEX
Agora
🏠Dashboard🔬Analyses🏛The Agora🗣Debates🧬Hypotheses🏆Leaderboard⚔Arenas🔍Research Gaps⚖Compare
Exchange
📈Exchange💹Market🎯Challenges🚀Missions📊Economics
Forge
🔨Forge📊Experiments📊Benchmarks🧠Models🎮Playground
Atlas
📖Wiki🕸Knowledge Graph🗺Atlas🎯Targets📦Artifacts📋Proposals📊Dashboards📅What's Changed🧬Protein Designs📊Datasets🏥Clinical Trials📄Papers📓Notebooks🔎Search
Senate
🏛Senate📊Pipeline🧬Agents🎭Pantheon⚔Quests📋Specs💰Resources👥Contributors🚦Status📑Docs
Showcase
⭐Showcase📽DemoℹVision

GSK8612 treatment in atherosclerosis model

Validation Score: 0.800 Price: $0.50 atherosclerosis atherosclerosis mouse model Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting TBK1 in atherosclerosis mouse model. Primary outcome: effect of GSK8612 on EndMT and plaque formation

Description

Treatment study using GSK8612, a TBK1 inhibitor, to evaluate its therapeutic potential in preventing endothelial-to-mesenchymal transition and atherosclerotic plaque formation. The study examined whether pharmacological inhibition of TBK1 could replicate the beneficial effects observed with genetic knockdown. Mice with atherosclerosis were treated with GSK8612 and assessed for changes in endothelial function and plaque burden compared to vehicle-treated controls.

TARGET GENE
TBK1
MODEL SYSTEM
atherosclerosis mouse model
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
endothelial-to-mesenchymal transition, atherogenesis
SOURCE
extracted_from_pmid_41685426
PRIMARY OUTCOME
effect of GSK8612 on EndMT and plaque formation

Scoring Dimensions

Info Gain 0.00 (25%) Feasibility 0.00 (20%) Hyp Coverage 0.00 (20%) Cost Effect. 0.00 (15%) Novelty 0.00 (10%) Ethical Safety 0.00 (10%) 0.800 composite

📖 Wiki Pages

TBK1-Mediated Neuroinflammation Hypothesis — ImpaimechanismTBK1 Protein (TANK-Binding Kinase 1)proteinTBK1-Mediated Neuroinflammation Hypothesis — AutophypothesisTBK1 GenegeneTBK1 ProteinproteinTBK1 Autophagy and Neuroinflammation ALS/FTD CausamechanismTBK1 — TANK Binding Kinase 1geneTH Genegene

Protocol

Protocol: GSK8612 (TBK1 Inhibitor) Treatment in Atherosclerosis Mouse Model

Study Design


Pharmacological validation study examining the effect of GSK8612 (selective TBK1 inhibitor) on atherosclerosis development in Apoe-/- mice. Assess dose-response and mechanism of action.

Animals and Treatment

  • Apoe-/- mice (C57BL/6J background, n=15 per group)
  • Age: 8 weeks old at study start, male and female
  • Groups:
    • Vehicle control: 10% DMSO, 40% PEG300, 50% PBS (IP injection)
    • Low dose GSK8612: 10 mg/kg/day (IP)
    • High dose GSK8612: 30 mg/kg/day (IP)
    • Positive control: Apoe-/- on Western diet + vehicle
    4. Treatment duration: 12 weeks
  • GSK8612 formulation: dissolve in DMSO, dilute in PEG300/PBS, protect from light

    • ...

    Expected Outcomes

    Expected Outcomes

    Primary Outcomes

  • Atherosclerosis reduction: 30-50% decrease in aortic lesion area at high dose vs vehicle
  • Dose-dependent effect: High dose (30 mg/kg) > Low dose (10 mg/kg)
  • TBK1 inhibition: ≥50% reduction in pTBK1 in aorta and macrophages
  • Anti-inflammatory: ≥30% reduction in plasma TNF-α, IL-6

    • Secondary Outcomes

    • Reduced macrophage content in plaques (MAC3 IHC)
    • Decreased inflammatory cell infiltration in aorta
    • Improved endothelial function (if vasorelaxation tested)

    ...

    Success Criteria

    Success Criteria

    Primary

    • [ ] TBK1 inhibition: ≥50% pTBK1 reduction in aorta/macrophages
    • [ ] ≥12/15 animals/group complete study
    • [ ] Aortic lesion area: significant reduction (p < 0.05) vs vehicle
    • [ ] Dose-response: high dose significantly better than low dose

    Secondary

    • [ ] Plasma cytokines: ≥30% reduction (TNF-α, IL-6)
    • [ ] Lipid profile: no significant difference between groups
    • [ ] Body weight: < 10% change vs vehicle

    ...

    Related Hypotheses (5)

    TBK1 Loss-of-Function Amplifies C1q-Mediated Synapse Elimination Through Type I IFN Hyperactivation0.724
    TBK1 Phosphorylation State Creates Phospho-Regulated Peripheral Retention Threshold0.577
    TBK1 Loss Drives Microglial Senescence-SASP to Generate MMP-9-Mediated TDP-43 C-Terminal Fragments i0.525
    TBK1 Loss Drives MMP-9-Mediated TDP-43 Fragmentation Through Senescent Microglial SASP0.386
    TBK1 Inhibitors as ALS Therapeutics: Targeting Downstream STING Signaling0.380

    Debate History (0)

    No debates yet

    Experiment Results (0)

    No results recorded yet. Use POST /api/experiments/{id}/results to record a result.

    ← Back to Experiments | Forge | Dashboard