Additional Research Compound · For laboratory research use only
Also known as O-304
ATX-304 (4-chloro-N-[2-[(4-chlorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide) is a small molecule first published as O304, a pan-AMP-activated protein kinase (AMPK) activator developed by Betagenon (later Amplifier Therapeutics)1. The ATX-304 name appears in more recent independent studies4,5.
Published research covers diet-induced obese and diabetic mice, aged mice, models of fatty liver disease and acute kidney injury, and nematode and isolated artery models1,2,3,4,5,6. Several of the studies were authored or supported by the developing company, as disclosed in the papers1,2,3,5.
As described in the research literature
As described in the research literature, O304 was identified as a pan-AMPK activator that increased glucose uptake in skeletal muscle and activated AMPK in the heart of mice1. In primary tubular epithelial cells, ATX-304 increased acetyl-CoA carboxylase phosphorylation, an index of AMPK activation, and its protective effect in a cisplatin injury model was lost in AMPK-null fibroblasts5.
Later work from the originating group reported that O304 also acts as a mitochondrial uncoupler, generating a metabolic demand that the authors linked to insulin-independent glucose uptake and utilisation in muscle and heart3. An independent 2025 study confirmed the uncoupling effect in vascular smooth muscle and liver cell lines, measuring increased oxygen consumption after ATP synthase inhibition and reduced mitochondrial membrane potential6. That study describes the AMPK activation as arising through inhibition of protein phosphatase 2C6.
What published studies have examined
Diet-induced obese mice were used to examine skeletal muscle glucose uptake, beta-cell stress, microvascular perfusion and cardiac function1. In db/db mice, studies examined insulin-independent glucose uptake, beta-cell mass and insulin content, and gene expression in muscle and heart3. The 2018 paper also reports a proof-of-concept phase IIa trial in people with type 2 diabetes receiving metformin1.
Aged mice were used to examine hyperinsulinaemia, insulin resistance, cardiac function and exercise capacity2. In C. elegans, lifespan was examined in relation to the AMPK-mTOR axis and autophagy, alongside senescence markers in mouse embryonic fibroblasts6.
A mouse model of progressive fatty liver disease examined body fat, blood cholesterol, steatosis, fibrosis, fatty acid oxidation and lipid distribution across liver lobes4. A cisplatin-induced acute kidney injury model in mice and primary tubular epithelial cell cultures examined serum creatinine, NGAL, histology, metabolomics and cellular respiration5.
Isolated rat mesenteric arteries were used to examine relaxation of phenylephrine and U46619-induced constriction, which the authors reported to be endothelium-independent6.
Sources [6]
PAN-AMPK activator O304 improves glucose homeostasis and microvascular perfusion in mice and type 2 diabetes patients.
Steneberg P, Lindahl E, Dahl U, et al. JCI Insight, 2018.
AMPK activator O304 improves metabolic and cardiac function, and exercise capacity in aged mice.
Ericsson M, Steneberg P, Nyrén R, et al. Communications Biology, 2021.
O304 ameliorates hyperglycemia in mice by dually promoting muscle glucose effectiveness and preserving β-cell function.
Norlin S, Axelsson J, Ericsson M, et al. Communications Biology, 2023.
AMPK activator ATX-304 reduces oxidative stress and improves MASLD via metabolic switching.
Holm E, Vermeulen I, Parween S, et al. JCI Insight, 2025.
The AMPK activator ATX-304 alters cellular metabolism to protect against cisplatin-induced acute kidney injury.
Katerelos M, Gleich K, Harley G, et al. Biomedicine & Pharmacotherapy, 2024.
O304 is a mitochondrial uncoupler which extends C. elegans lifespan and induces vasorelaxation of rat mesenteric arteries.
Li WF, Zeng Y, Zhang YD, et al. Chemico-Biological Interactions, 2025.
This page is provided for research and educational reference only. It does not constitute medical advice, dosing guidance, or a recommendation for use. All compounds are strictly for laboratory and in-vitro research purposes.