ATX-304 100mg x 60 Tablets
A first-in-class oral small-molecule pan-AMPK and mitochondrial activator currently in Phase 2 clinical development for cardiometabolic diseases—designed to mimic the cellular energy-sensing benefits of exercise at the molecular level.
The Science
What is ATX-304?
ATX-304 (formerly designated O304) is a synthetic small-molecule compound developed by Amplifier Therapeutics as a pan-AMPK (AMP-activated protein kinase) activator. AMPK is often called the cell's 'master energy switch'—a kinase complex that is activated during metabolic stress such as exercise or caloric restriction and subsequently orchestrates broad metabolic reprogramming. ATX-304 activates all known AMPK complexes simultaneously, earning its classification as a pan-AMPK activator.
Unlike earlier AMPK-targeting compounds, ATX-304 is orally bioavailable and has demonstrated activity not only on AMPK but also on mitochondrial function directly, influencing oxidative phosphorylation and reducing oxidative stress. In preclinical models, the compound improved glucose homeostasis, microvascular perfusion, and liver fat accumulation (MASLD) through a process of metabolic switching from lipid storage toward fatty-acid oxidation.
ATX-304 is currently in Phase 2 clinical trials for cardiometabolic disease indications including obesity and metabolic-dysfunction-associated steatotic liver disease (MASLD). Research published in JCI Insight (2025) demonstrated that ATX-304 reduces hepatic oxidative stress and improves MASLD markers in preclinical models by reprogramming cellular energy metabolism—independent of dietary intervention.
Laboratory Observations
Research-Observed Areas of Interest
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Preclinical research published in JCI Insight (2025) found ATX-304 significantly reduced hepatic steatosis, oxidative stress markers, and liver inflammation by reprogramming tubular and hepatic cell metabolism.
Obesity and Body Composition
Phase 1 clinical data suggest ATX-304 may support reductions in body fat mass through AMPK-driven inhibition of lipogenesis and enhancement of fatty-acid oxidation, without the appetite-suppressive profile of GLP-1 agonists.
Glycemic Control
Studies in type 2 diabetes research subjects (O304 precursor data, published in JCI 2018) demonstrated improved fasting glucose and HbA1c-related metabolic markers, attributed to enhanced peripheral glucose uptake.
Renal Protection
A study in the Journal of the American Society of Nephrology (2023) found ATX-304 reprogrammed tubular cell metabolism to protect against cisplatin-induced acute kidney injury in preclinical models.
Exercise Mimicry in Aging
Research in aged mice demonstrated that ATX-304 improved metabolic, cardiac, and vascular function in a manner resembling the physiological benefits of regular exercise—positioning it as a potential research tool for age-related metabolic decline.
Mechanism of Action
How ATX-304 Works
ATX-304 exerts its effects through three interconnected mechanisms centered on AMPK activation and mitochondrial engagement:
Pan-AMPK Network Activation
ATX-304 binds to and activates all heterotrimeric AMPK complexes (α1β1γ1, α2β2γ1, and related variants), triggering a downstream signaling cascade that inhibits anabolic processes (fatty-acid synthesis, gluconeogenesis) and promotes catabolic ones (fatty-acid oxidation, glucose uptake). This broad AMPK engagement distinguishes it from isoform-selective activators.
Mitochondrial Metabolic Switching
Research suggests ATX-304 directly improves mitochondrial function by promoting oxidative phosphorylation efficiency and reducing the production of reactive oxygen species (ROS). In liver models, this translates to a metabolic shift away from lipid accumulation toward fat combustion, a mechanism implicated in its anti-MASLD activity.
Glucose Homeostasis and Microvascular Perfusion
In both preclinical studies and early human translational data, ATX-304 improved insulin sensitivity and glucose uptake in peripheral tissues, while also enhancing microvascular blood flow—a cardiovascular benefit attributed to AMPK-driven endothelial nitric oxide synthase (eNOS) activation.
FAQ
Frequently Asked Questions
What makes ATX-304 different from metformin or other AMPK activators?+
Metformin activates AMPK indirectly by inhibiting Complex Research indicates of the mitochondrial respiratory chain, which raises the AMP:ATP ratio. ATX-304 activates AMPK directly and pan-selectively across all complex variants, and also engages mitochondrial function through additional mechanisms—potentially offering broader and more targeted metabolic effects.
What conditions is ATX-304 being studied for?+
Current and recent clinical programs are investigating ATX-304 for cardiometabolic diseases including obesity, metabolic-dysfunction-associated steatotic liver disease (MASLD), and type 2 diabetes-related metabolic dysfunction.
Research-Only Notice
ATX-304 100mg x 60 Tablets is categorized by the FDA as for research-purposes-only. It is not intended for human consumption, diagnosis, treatment, cure, or prevention of any disease. The information above summarizes effects observed in laboratory studies to date and is provided strictly for scientific and educational reference.