ATX-304 (O-304)
Research Guide

Research Overview

ATX-304 (also referenced as O-304) is a small-molecule pan-AMPK activator studied as a laboratory tool compound in cell-culture and animal metabolism research. It belongs to the 1,2,4-thiadiazole benzamide chemotype and is not a peptide, which distinguishes its handling and identity profile from the lyophilized peptides in the catalog.

In the published literature it is described as a direct, broadly-acting activator of the AMP-activated protein kinase (AMPK) heterotrimeric complex rather than an isoform-selective activator. Investigators have used it as a probe for AMPK signaling, mitochondrial function, and exercise-mimetic metabolic switching across a range of preclinical models.

This page summarizes verified identity data and reported research findings for reference only. All statements describe in-vitro and preclinical research context. Nothing here describes human use, dosing for people, or any therapeutic or diagnostic application.

Mechanism Summary

Mechanisms reported in the in-vitro and preclinical research literature include:

• Reported mechanism, described from in-vitro and preclinical work only: ATX-304 (O-304) is characterized as a direct pan-AMPK activator, meaning it is reported to activate AMPK heterotrimer complexes broadly rather than selectively targeting a single isoform.
• The recurring mechanistic account is that ATX-304 activates AMPK by suppressing dephosphorylation of the activation-loop threonine-172 (Thr172), which stabilizes the active phosphorylated kinase. AMPK activation in these studies is read out by increased phosphorylation of the downstream substrate acetyl-CoA carboxylase (ACC).
• Downstream of AMPK activation, the literature reports a shift away from anabolic pathways such as hepatic de novo lipogenesis and cholesterol synthesis and toward catabolic pathways such as fatty-acid beta-oxidation, framed as an exercise-mimetic metabolic switch. A separately reported mechanism is increased cellular respiration through mitochondrial uncoupling, including an approximately 38% increase in basal oxygen consumption rate in tubular epithelial cells (PMID 38749175), with AMPK-dependence demonstrated by loss of effect in AMPK-null cells (PMID 38749175).
• All mechanistic descriptions above are drawn from cell-culture and animal studies plus one early proof-of-concept human study. No human efficacy is established, and none of these findings should be read as a claim about effects in people.

Reference Data

Identity values are compiled from public chemistry databases and vendor documentation. Confirm the exact salt form, molecular weight, and purity for a given batch against its Certificate of Analysis (COA).

Research Applications

In laboratory research, ATX-304 (O-304) is studied in contexts such as:

• Studied in a proof-of-concept phase IIa clinical study in type 2 diabetes patients already on metformin, where reduced fasting plasma glucose and HOMA-IR were reported (PMID 29925691). This is a reported research finding only, not an approved indication and not a human-use claim.
• Investigated in diet-induced obese mice for glucose homeostasis, with reported increased skeletal-muscle glucose uptake, reduced beta-cell stress, and promotion of beta-cell rest (PMID 29925691).
• Investigated for microvascular and cardiovascular endpoints in mice and in the same type 2 diabetes cohort, with reported improved peripheral microvascular perfusion and reduced blood pressure; in mice, reported increased cardiac AMPK activation, cardiac glucose uptake, reduced cardiac glycogen, and improved left-ventricular stroke volume without increased heart weight (PMID 29925691).
• Studied in aged mice as a model of metabolic aging, with reported improvements in metabolic and cardiac function and exercise capacity (PMID 34795407).
• Investigated in a preclinical mouse model of MASLD / progressive fatty liver disease (choline-deficient high-fat diet), with reported reduced body fat mass, lowered blood cholesterol, mitigated hepatic steatosis and fibrosis progression, reduced oxidized lipids, and a metabolic shift toward beta-oxidation (PMID 40197369).
• Investigated as a protective agent in a cisplatin-induced acute kidney injury mouse and tubular-epithelial-cell model, with reported AMPK-dependent metabolic reprogramming and reduced markers of kidney injury including serum creatinine, NGAL, and histological injury (PMID 38749175).
• Studied for epigenetic and transcriptional effects in pancreatic islets of diet-induced obese mice, with reported prevention of gene-expression changes and remodeling of histone marks (PMID 34949756).
• Used as a research tool compound for probing AMPK signaling, mitochondrial uncoupling, and exercise-mimetic metabolic switching in cellular and animal metabolism studies.

Storage Information

• As a small-molecule solid, ATX-304 is generally handled as a dry powder. Literature and supplier ranges vary, so confirm the storage temperature and shelf life for this specific product against the batch COA before use.
• Supplier pages cite solubility of approximately 10 mM in DMSO for stock preparation. Confirm the reconstitution solvent and working-stock stability for the catalog product against its own COA or handling sheet.
• For general handling of stored research materials, see the Lyophilized Storage Guide. Note that lyophilized-peptide handling conventions do not map one-to-one onto a small-molecule powder, so treat the peptide guidance as background context and defer to the COA for this compound.
• For preparing working concentrations from a DMSO or other solvent stock, the Reconstitution Calculator can help convert between mass, volume, and molarity. Use the confirmed molecular weight of approximately 380.2 g/mol as the input.