What is ATX-304?
ATX-304 (O304) is a synthetic small molecule that activates AMP-activated protein kinase (AMPK), the cell's energy sensor. Researchers at Umeå University and Betagenon AB in Sweden found it in a cell-based screen and called it a pan-AMPK activator (Steneberg et al., 2018).
Later papers use the code ATX-304: one calls it "formerly O304" (Holm et al., 2025), and another says Amplifier Therapeutics (Betagenon) supplied it (Katerelos et al., 2024). It is investigational, with no approval as a medicine. Disguised Alpha supplies it as the sodium salt in 50MG capsules, 60 capsules per bottle, for laboratory research use only. Nothing on this page is guidance for use in people.
ATX-304 reference data
| Property | Value |
|---|---|
| Name | ATX-304 (Sodium Salt) |
| Also called | O304, O-304, pan-AMPK activator O-304 (PubChem CID 50923806); O304 sodium (PubChem CID 167314152) |
| Structure | 4-chloro-N-[2-[(4-chlorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide: a thiadiazolone ring with 4-chlorobenzyl and 4-chlorobenzamide groups |
| Compound class | Small-molecule pan-AMPK activator, also reported to act as a mitochondrial uncoupler |
| Molecular formula | C₁₆H₁₁Cl₂N₃O₂S (free compound); sodium salt C₁₆H₁₀Cl₂N₃NaO₂S |
| Molecular weight | 380.2 g/mol (free compound); sodium salt 402.2 g/mol |
| Form | Capsules, 50MG per capsule, 60 capsules per bottle (3,000MG per bottle) |
| Testing | Third-party tested, with the certificate for each lot published on the product page and in the COA portal |
Format, strength and storage are from the ATX-304 product page, whose lot certificate reports HPLC identity as O-304. The page lists C₁₆H₁₁Cl₂N₃O₂S and 380.2 g/mol, which PubChem CID 50923806 gives for the free compound; that record is also the source of the aliases and structure. For the sodium salt, PubChem CID 167314152 gives C₁₆H₁₀Cl₂N₃NaO₂S, 402.2 g/mol; use the lot certificate for the measured content.
See it beside the other compounds on this site in the peptide molecular weight reference table.
What the research covers
Published work on ATX-304 and O304 falls into six areas. Apart from one 28-day trial, the evidence comes from cells, tissues and animals, and six of the eleven primary papers involve Betagenon through a co-founder author or supplied compound.
Discovery and mechanism
The discovery paper reported that O304 raised AMPK phosphorylation at threonine 172 in cells without lowering cellular ATP. In cell-free assays it suppressed PP2C-mediated dephosphorylation of that site on human AMPK trimers without inhibiting PP2C itself, and it did not activate AMPK allosterically. In cells it needed the upstream kinase LKB1 and worked with either β1 or β2 subunits (Steneberg et al., 2018).
The same group later reported mitochondrial uncoupling in myotubes (Norlin et al., 2023), and an independent group confirmed it in A10 and HepG2 cells, where it lowered mitochondrial membrane potential and activated AMPK (Li et al., 2025). Models: recombinant protein, cell lines and myotubes.
Glucose control and beta cells in diabetic mouse models
In diet-induced obese mice gavaged with 100 mg/kg per day for 8 weeks, O304 alone or with metformin prevented the rise in fasting glucose, insulin and HOMA-IR, and in the diet it reduced islet amyloid in hIAPP transgenic mice (Steneberg et al., 2018).
In CBA mice on a high-fat diet, it largely prevented diet-linked changes in islet gene expression and chromatin marks, including the beta-cell stress marker Aldh1a3 (López-Pérez et al., 2021). In streptozotocin diabetic mice it raised muscle glucose uptake, restored heart glucose uptake and lowered glycogen build-up, and in db/db mice it preserved beta-cell mass and insulin secretion (Norlin et al., 2023). Models: mice and islets.
Heart and blood vessels
In diet-induced obese mice fed O304, cardiac glucose uptake rose, heart glycogen fell and stroke volume rose by about 20%, with no increase in heart weight; rats gavaged for six months at 100 to 600 mg/kg per day showed no rise in heart-to-brain weight ratio (Steneberg et al., 2018).
In streptozotocin diabetic mice, one week on an O304 diet raised the E/A ratio and shortened isovolumetric relaxation time, which the authors call reversal of diabetic cardiomyopathy (Norlin et al., 2023). In ApoE-deficient mice given angiotensin II, 200 mg/kg orally reduced aneurysm formation and blood pressure (Sun et al., 2024). Models: mice and rats.
Aging models
In male F1 hybrid mice fed O304 from 6 or 12 months of age, it prevented and reversed age-associated insulin resistance, raised stroke volume and cardiac output on echocardiography, raised myocardial capillary density and lengthened treadmill running distance to exhaustion. Heart weight was 15% higher after six months, without more fibrosis or glycogen, and the authors call O304 an exercise mimetic (Ericsson et al., 2021).
In 18-month-old mice with one kidney removed, 10 mg/kg per day intraperitoneally for 12 weeks reduced renal senescence and fibrosis markers (Zhu et al., 2022). At 100 micromolar it extended C. elegans lifespan through the AMPK-mTOR axis (Li et al., 2025). Models: mice and nematodes.
Liver, kidney injury and pain models
In male C57BL/6J mice on a choline-deficient high-fat diet, a model of fatty liver disease (MASLD), ATX-304 at 1 mg/g of diet for 7 to 24 weeks reduced steatosis and fibrosis development and lowered blood cholesterol, with more fatty acid oxidation and uneven effects between liver lobes (Holm et al., 2025).
Mice fed ATX-304 chow for 7 days before cisplatin had lower serum creatinine, NGAL and histological injury, and its protection of cultured cells was lost in AMPK-null fibroblasts (Katerelos et al., 2024). In mouse pain models, 200 mg/kg by gavage reduced mechanical hypersensitivity after hind-paw incision (Das et al., 2019) and allodynia after lumbar disk puncture, with an ED50 of 140 mg/kg (Das et al., 2022). Models: mice and kidney cells.
The phase IIa trial in type 2 diabetes
The only published human data come from TELLUS, an exploratory, randomized, double-blind 28-day phase IIa study comparing one daily amount of O304 with placebo in 65 people with type 2 diabetes on metformin (Steneberg et al., 2018). In a post hoc subgroup, fasting glucose fell by 0.60 mmol/L on O304 versus 0.10 on placebo.
Across the O304 group, systolic and diastolic blood pressure fell by 5.8 and 3.8 mmHg against small rises on placebo, and MRI showed more calf muscle perfusion. The authors called the glucose change modest, noted a weight imbalance between groups, and reported O304 as well tolerated. Model: people with type 2 diabetes.
Key studies
- Steneberg P, et al. JCI Insight. 2018. PMID 29925691. DOI 10.1172/jci.insight.99114. Discovery paper: cell-free assays, diabetic mice, rats, dogs and the TELLUS phase IIa trial, with lower fasting glucose in a post hoc subgroup; Betagenon founders and staff among the authors.
- Ericsson M, et al. Commun Biol. 2021. PMID 34795407. DOI 10.1038/s42003-021-02837-0. Aging male F1 mice: insulin resistance, echocardiography and treadmill running, with exercise-like cardiac changes.
- Norlin S, et al. Commun Biol. 2023. PMID 37626210. DOI 10.1038/s42003-023-05255-6. Streptozotocin and db/db mice plus myotubes: glucose uptake, mitochondrial uncoupling and beta-cell function.
- Katerelos M, et al. Biomed Pharmacother. 2024. PMID 38749175. DOI 10.1016/j.biopha.2024.116730. Cisplatin kidney injury in mice and cells, with AMPK-dependent protection.
- Holm E, et al. JCI Insight. 2025. PMID 40197369. DOI 10.1172/jci.insight.179990. Choline-deficient high-fat diet mice: less steatosis and fibrosis.
- Li WF, et al. Chem Biol Interact. 2025. PMID 41130350. DOI 10.1016/j.cbi.2025.111788. Cell lines, C. elegans and rat arteries: independent confirmation of uncoupling.
Handling and storage of ATX-304 capsules
General laboratory practice for this material:
- Store the sealed capsules at 15 to 25°C in the original container, away from moisture and direct light (per the product page).
- Capsules ship in a sealed bottle or a resealable pouch, depending on the batch; close it fully after each opening.
- Record the lot number and keep its certificate, which reports the measured content per capsule for that lot.
- For identity checks, allow for the salt form: 380.2 g/mol as the free compound, 402.2 g/mol as the sodium salt.
Frequently asked questions
What is ATX-304?
A synthetic small molecule, first reported as O304, that activates AMPK (Steneberg et al., 2018) and uncouples mitochondria (Norlin et al., 2023).
Is ATX-304 the same as O304?
Yes. A 2025 study calls ATX-304 "formerly O304" (Holm et al., 2025), matching the identity data earlier work gives for O304 from Betagenon (Ericsson et al., 2021).
Is ATX-304 a peptide?
No. It is a small synthetic molecule built on a thiadiazolone ring with two chlorophenyl groups and no amino acids (PubChem CID 50923806). Its developers summarize it as a small molecule (Norlin et al., 2023).
How does the AMPK activator O304 work?
As reported, it shields the activating phosphorylation of AMPK at threonine 172 from removal by PP2C, without allosteric activation (Steneberg et al., 2018), and it uncouples mitochondria (Li et al., 2025). A 2026 review groups it with ADaM-site activators (Amatya et al., 2026), but its developers contrast it with that class (Norlin et al., 2023).
Has ATX-304 been tested in people?
Only in early studies: a phase I safety study, which the discovery paper mentions as completed without giving data, and the 28-day TELLUS phase IIa trial in type 2 diabetes, reported in that paper (Steneberg et al., 2018). No later trial reports appear in PubMed. It remains investigational; a 2025 study noted that no direct AMPK activator had reached the market (Holm et al., 2025).
Is ATX-304 on the WADA Prohibited List?
Its class is. The 2026 WADA Prohibited List prohibits "Activators of the AMP-activated protein kinase (AMPK)" at all times under S4.4.1, metabolic modulators. It names examples such as AICAR and MOTS-c, not O304 or ATX-304, but the papers above describe ATX-304 as an AMPK activator.
Where can researchers buy ATX-304?
Disguised Alpha sells it for laboratory research as 50MG capsules, 60 per bottle, listed as the sodium salt and third-party tested: ATX-304 (Sodium Salt). A liquid blend with 10MG/ML ATX-304 and 20MG/ML 5-Amino-1MQ in 20ML is listed as MitoX (ATX-304 / 5-Amino-1MQ).
Related compounds and guides
- MitoX research guide
- 5-Amino-1MQ research guide
- MOTS-c research guide
- MOTS-c vs 5-Amino-1MQ: research comparison
- NAD+ research guide
- SLU-PP-915 capsules research guide
- SLU-PP-332 research guide
- COA portal
This product is for research use only. It has not been evaluated for safety or effectiveness in humans. Not for human consumption. All products are intended for laboratory research purposes only.