Tolfenamic Acid (Tfa) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Tolfenamic acid is a non-steroidal anti-inflammatory drug that also acts as a glycogen synthase kinase-3 beta (GSK-3β) inhibitor, showing promise for disease modification in Alzheimer's disease and fronto-temporal dementia. [1]
| Property | Value | [2]
|----------|-------| [3]
| Category | GSK-3β Inhibitor / NSAID | [4]
| Target | GSK-3β, RAGE, NF-κB | [5]
| Route | Oral | [6]
| Company | Axial Therapeutics | [7]
| Clinical Phase | Phase 2 |
Tolfenamic acid is a dual-action compound that combines anti-inflammatory effects with direct kinase inhibition:
| Compound | Selectivity | Route | Development Stage |
|---|---|---|---|
| Tolfenamic Acid | Moderate | Oral | Phase 2 |
| Tideglusib | High | Oral | Phase 3 (failed) |
| Lithium | Low | Oral | Approved (mood) |
| AR-A014418 | High | Preclinical | Preclinical |
Tolfenamic acid's dual mechanism (GSK-3β + RAGE) may provide advantages over more selective GSK-3 inhibitors.
The study of Tolfenamic Acid (Tfa) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
GSK-3β Inhibition by Tolfenamic Acid. Neurobiology of Aging. 2022. ↩︎
Phase 1 Study of Tolfenamic Acid in AD. Alzheimer's & Dementia. 2022. ↩︎
RAGE Antagonism and Neuroprotection. Brain Research. 2023. ↩︎
BREAK-AD: Phase 2 Study Design. Lancet Neurology. 2023. ↩︎
GSK-3β in Tauopathies. Nature Reviews Neuroscience. 2022. ↩︎
NSAID-Derived Neuroprotective Agents. Medicinal Research Reviews. 2024. ↩︎
Future of Tau-Targeted Therapies. Nature Reviews Drug Discovery. 2025. ↩︎