Pan-AMPK activation
In laboratory work, O-304 protects phosphorylated AMPK from dephosphorylation, increasing pathway activity across AMPK complexes. Mechanistic study.
Back to Peptide Library
Metabolic Small Molecule
O-304
ATX-304 • Oral Pan-AMPK & Mitochondrial Research
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
O-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
- 50–400 mg dailyAnecdotal; no validated retail dose
- Research target
- AMPK networkMetabolic signaling and energy expenditure
Overview
What Is O-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
O-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
O-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
O-304 Dosing Protocol
Trial doses belonged to specific formulations: legacy O-304 suspension at 1,000 mg daily for 28 days and ATX-304 sodium-salt tablets at 400 mg daily for eight weeks.
Community oral range50–400 mg daily
- Clinical ATX-304
- 400 mg sodium-salt tablet daily for eight weeks in Phase 1b.
- Legacy O-304
- 1,000 mg suspension daily for 28 days in TELLUS.
- Retail context
- Capsule or powder identity and bioavailability may differ from both trial formulations.
- Evidence boundary
- No FDA-approved human dose, cycle, or long-term use schedule.
N=1 reports
O-304 Community Experience
These are self-reported experiences, not controlled findings. Product identity, dose, and outcomes cannot be verified from anecdotes.
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
O-304 Stacking & Synergy
No O-304 combination protocol has been validated in people. Pathway comparisons do not establish synergy or safety, particularly alongside glucose-lowering treatments.
O-304 + SLU-PP-915
AMPK and ERR signaling are distinct metabolic targets. This is a theoretical pairing without controlled combination data.
O-304 + MOTS-c
Both are discussed around AMPK and metabolic adaptation. Overlap may make effects harder to attribute.
O-304 + Retatrutide
Different metabolic and appetite pathways invite interest, but human combined-use evidence is absent and glucose effects require care.
Safety notes
O-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.
O-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 O-304
Not medical advice. This editorial is our own opinion piece based off the experience of our own lab rats.
Our opinionated opinion
We see O-304 as one of the more interesting metabolic research compounds in this space. The AMPK and mitochondrial story offers a different angle from appetite-focused agents such as Retatrutide, while people in the community often describe the effect as subtler than a stimulant or GLP-1 drug.
In our experience and community feedback, some notice better endurance or metabolic flexibility; others see little beyond mild GI discomfort. We regard it as a niche tool that makes the most sense alongside actual training and nutrition, not a substitute for them. The clinical signals are promising, but product identity and long-term safety still limit practical confidence.