ATX-304

What Is ATX-304?

ATX-304 is a small molecule developed by Betagenon Sweden AB, designed to activate AMPK, an enzyme that acts as the cell's internal energy sensor and plays a central role in glucose metabolism, fat oxidation, and mitochondrial function. AMPK activation is also involved in metformin's metabolic effects, but ATX-304 gets there through a different route.

Where metformin activates AMPK indirectly by raising cellular AMP levels, ATX-304 works by preventing dephosphorylation at the Thr172 site on AMPK's alpha subunit, keeping the enzyme active through a distinct mechanism. Research has also found mild mitochondrial uncoupling as a secondary metabolic effect.

What ATX-304 Is Being Researched For

• Blood Sugar Control in Type 2 Diabetes

  A completed 28-day human Phase IIa trial in people with type 2 diabetes already taking metformin found improvements in blood glucose, blood pressure, and microvascular perfusion.^[1]

• Metabolic Dysfunction-Associated Liver Disease

  A preclinical mouse study found reduced body fat mass, lower blood cholesterol, and mitigation of liver steatosis and fibrosis progression, alongside a shift toward increased fatty acid oxidation and reduced lipid synthesis.^[2]

• Kidney Protection

  Research found protection against cisplatin-induced acute kidney injury in animal models and cultured kidney cells, linked to reduced energy stress and mitochondrial changes.^[3]

How ATX-304 Works

• Locking AMPK in Its Active State

  Research points to ATX-304 preventing removal of a phosphate group at the Thr172 site on AMPK's alpha subunit, keeping the enzyme active longer. This is mechanistically distinct from metformin's indirect activation.^[3]

• Mild Mitochondrial Uncoupling

  Research points to a secondary effect in which ATX-304 mildly uncouples mitochondrial energy production and increases oxygen consumption independent of its AMPK-activating signal.^[3]

• Exercise-Mimetic Effects in Animal Models

  In obese mice, ATX-304 produced some effects that parallel exercise, including increased energy expenditure and exercise capacity alongside reduced fat mass.

Reconstitution and Handling

ATX-304 is typically supplied in capsule form for oral research use. Capsules should be stored in a cool, dry place away from direct light and handled according to the specific product's labeling since formulations can vary by supplier.

Key Takeaways

ATX-304 stands out for reaching a completed human Phase IIa trial, more advanced clinical evidence than most compounds in this category, while working through an AMPK-activation mechanism distinct from metformin's. Its broader research base spans liver disease, kidney protection, and exercise-related metabolic effects in animal models; body-composition-specific findings remain preclinical.

Frequently Asked Questions

Sources and Research

1. Betagenon Sweden AB. Phase IIa clinical trial of ATX-304 (O304) in type 2 diabetes patients on metformin therapy.
2. Öberg AI, et al. AMPK activator ATX-304 reduces oxidative stress and improves MASLD via metabolic switching. iScience. 2024.
3. Salt IP, et al. The AMPK activator ATX-304 alters cellular metabolism to protect against cisplatin-induced acute kidney injury. Biomed Pharmacother. 2024.