GKT137831 — The Dual NOX1/4 Inhibitor
GKT137831, also known as Setanaxib, is a targeted inhibitor of NOX1 and NOX4 enzymes, which are key drivers of oxidative stress and fibrosis. Its relevance to longevity lies in its potential to mitigate age-related tissue scarring and oxidative damage, though it remains an experimental compound primarily studied for specific fibrotic diseases.
Mechanism of Action
GKT137831 (Setanaxib) is a first-in-class dual inhibitor of NADPH oxidases 1 and 4 (NOX1/4). By blocking these enzymes, it directly reduces the production of reactive oxygen species (ROS) that drive oxidative stress and cellular damage. In preclinical models, inhibiting NOX1/4 attenuates fibrotic pathways, reduces inflammation, and prevents apoptosis in various tissues, including the liver, kidneys, and lungs. Its longevity relevance stems from its potential to mitigate age-related oxidative damage and fibrotic diseases, though its systemic anti-aging mechanisms in humans are poorly characterised.
Human Trial Evidence
No published human longevity trials. Animal/in-vitro evidence only. Setanaxib has advanced to Phase II clinical trials for primary biliary cholangitis and Alport syndrome, demonstrating safety and targeted biomarker improvements, but its effects on human aging remain unstudied.
Dosing Protocol
Dosing in clinical trials for primary biliary cholangitis and Alport syndrome typically ranges from 400 mg once daily to 400 mg twice daily. As an experimental therapeutic, optimal dosing for longevity or general health is unestablished in humans.
Safety & Contraindications
Clinical trials indicate Setanaxib is generally well-tolerated at tested doses, though long-term safety profiles are not fully established. Potential adverse effects, contraindications, and drug interactions remain under investigation. It should be avoided outside of clinical trials due to the lack of comprehensive safety data in healthy populations.