Pan-AMPK activation
In laboratory work, O-304 protects phosphorylated AMPK from dephosphorylation, increasing pathway activity across AMPK complexes. Mechanistic study.
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Metabolic Small Molecule
ATX-304 (O-304)
Formerly O-304 • Oral Pan-AMPK & Mitochondrial Research
ATX-304, formerly O-304, is an investigational oral small molecule, not a peptide. Human studies of legacy O-304 and the newer ATX-304 formulation report metabolic signals, but their doses and exposure are not interchangeable.
At a glance
ATX-304 Quick Reference
- Evidence stage
- Early human trialsTELLUS Phase 2a and ATX-304 Phase 1b
- Available format
- Oral capsuleRetail form differs from tested clinical formulations
- Community oral range
- Members onlySign in to view dosing details.
- Research target
- AMPK networkMetabolic signaling and energy expenditure
Overview
What Is ATX-304?
O-304 is a synthetic small molecule that increases activity across the AMP-activated protein kinase (AMPK) network. AMPK helps regulate fuel use, glucose uptake, and responses to cellular energy demand. Despite its place in peptide catalogs, O-304 is not a peptide.
The older O-304 suspension was studied in adults with type 2 diabetes. The newer ATX-304 sodium-salt tablet is part of the same development program, but its formulation and exposure differ. A milligram amount from either trial cannot be transferred directly to a retail capsule. TELLUS report · ATX-304 abstract.
Mechanism
ATX-304 Mechanism of Action
Mitochondrial demand
Later preclinical work found increased mitochondrial respiration and proton leak. This may contribute to energy expenditure, but the size of each mechanism's contribution in people is unresolved. Research abstract.
Glucose utilization
Cell and animal research found greater glucose uptake and oxidation in muscle and heart. The older human trial also explored glucose control in adults taking metformin.
Peripheral effects
Metabolic and vascular effects are being studied outside appetite-centered pathways. This is distinct from claiming that a capsule can replace exercise or treat obesity.
Research findings
ATX-304 Benefits
The evidence comes from a 28-day O-304 trial in type 2 diabetes and a small eight-week ATX-304 Phase 1b study in obesity with prediabetes.
Current evidence level: Small human trials
Resting metabolism
The 2026 ATX-304 abstract reported an increase in resting metabolic rate after eight weeks; this was an exploratory endpoint in 23 participants. Phase 1b abstract.
Visceral and liver fat
That study reported reductions from baseline in MRI-measured visceral and liver fat. Larger placebo-controlled studies are needed.
Glucose research
The TELLUS study reported improved fasting glucose and insulin-resistance measures in some analyses; not every placebo comparison was significant. Trial report.
Lipid markers
Early ATX-304 results reported lower triglycerides and higher adiponectin. Clinical significance over longer periods remains unknown.
Vascular research
Legacy O-304 work found greater calf-muscle microvascular perfusion and lower blood pressure in the studied diabetes population.
Exercise-related models
Animal experiments examined energy use and exercise capacity. Equivalent performance benefits have not been demonstrated in people.
Protocol planning
ATX-304 Dosing Protocol
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N=1 reports
ATX-304 Community Experience
Self-reported anecdotal experiences aggregated from public & private peptide community discussions and anonymous peptideprotocols.app user reports. This information does not carry the same weight as published research.
Positive reports
- Endurance. Some describe better tolerance for cardio.
- Energy. A subtle lift or warmer body temperature is reported.
- Glucose readings. A few report lower meter readings, though uncontrolled tracking cannot establish cause.
Negative reports
- Subtle or absent effects. Training, diet, and other compounds confound impressions.
- GI discomfort. Nausea or stomach upset are reported as amounts rise.
- Product uncertainty. O-304 and ATX-304 labels do not guarantee the same form or exposure.
Stacking & synergy
ATX-304 Stacking & Synergy
No ATX-304 combination protocol has been validated in people. Pathway comparisons do not establish synergy or safety, particularly alongside glucose-lowering treatments.
ATX-304 + SLU-PP-915
A pairing aimed at energy use and exercise adaptation. ATX-304 targets AMPK and mitochondrial activity, while SLU-PP-915 activates ERR-controlled genes involved in oxidative metabolism. The rationale is complementary signaling; added benefits from combining them remain untested.
ATX-304 + 5-Amino-1MQ
This pairing approaches metabolic regulation through different targets. ATX-304 influences AMPK and mitochondrial energy handling, while 5-Amino-1MQ inhibits NNMT, an enzyme involved in nicotinamide metabolism and fat-cell biology. The rationale is complementary metabolic signaling, but added benefits and safety from combining them have not been established.
ATX-304 + Retatrutide
This pairing explores energy expenditure alongside appetite and glucose regulation. Retatrutide acts through GLP-1, GIP, and glucagon receptors, while ATX-304 targets cellular energy handling. ATX-304 has been explored with semaglutide in preclinical research, but that does not establish benefits or safety with retatrutide.
Safety notes
ATX-304 Side Effects & Safety
Short human studies reported generally mild adverse events, but they were too small and brief to define long-term safety or the risks of unverified retail products.
Common or reported effects
- GI discomfort, nausea, or appetite changes.
- Lightheadedness, especially if blood pressure falls.
- Sleep disruption or unusual warmth in community reports.
Higher-concern signals
- Unexpected glucose lowering with diabetes medication.
- Persistent tingling, burning, or numbness reported anecdotally, not established as a trial signal.
- Palpitations, chest discomfort, fainting, or sustained temperature elevation need prompt assessment.
ATX-304 Precautions
Major interaction concerns
- Insulin, metformin, GLP-1 drugs, SGLT2 inhibitors, and other glucose-lowering therapies warrant clinical review.
- Blood-pressure medication or a history of hypotension may complicate interpretation.
- Unknown product identity or purity is a material safety gap.
Conditions needing caution
- Pregnancy or breastfeeding: reproductive safety has not been established.
- Cardiovascular, liver, kidney, or metabolic illness needs individualized evaluation.
- Other AMPK activators or mitochondrial uncouplers may create overlapping effects.
Regulatory status: O-304 and ATX-304 remain investigational and are not FDA approved for human use.
Final verdict
Peptide Protocols Verdict on ATX-304
Not medical advice. This editorial is our own opinion piece based off the experience of our own lab rats.
Our opinionated opinion
We’re using ATX-304 right now, and we like it. MOTS-c gave us the training energy and endurance we were looking for, but persistent injection-site reactions eventually made it more trouble than it was worth. That sent us looking for an oral alternative. ATX-304 is now part of our replacement stack alongside SLU-PP-915 and PQQ, and so far we’ve been pleased with how we feel during training. Because we’re using them together, we can’t credit ATX-304 alone for those results.
The science gives us another reason to keep an eye on it. Early human research reports higher resting metabolic rate and reductions in liver and visceral fat. That makes it an interesting potential companion to a GLP-1: appetite control alongside a different approach to energy expenditure. In obese mice, ATX-304 combined with semaglutide produced greater weight loss than semaglutide alone, with no measured loss of lean mass in the combination group. Those are encouraging preclinical findings, not proof that adding ATX-304 improves weight loss or preserves muscle in people.
Yes, it’s niche, but it definitely has a place in a stack—especially for someone who likes MOTS-c but finds the injection-site reactions too much. We see it as a practical alternative to explore, not a proven like-for-like replacement. The main downside for us is the price. The upside is convenience: it’s a capsule, so no needles or injection-site reactions from taking it. For us, that tradeoff has made it worth keeping in the rotation.