Educational reference only. Nothing on this page constitutes medical advice or encourages personal use of this compound. Always consult a qualified healthcare provider before any decision involving your health.

ATX-304

Animal replicated

Research chemicalPan-AMPK Activator Small Molecule Mitochondrial Uncoupler

RouteOralGray-market only

Evidence grade: Animal replicated

Effect demonstrated in multiple animal studies; human data sparse or extrapolated. Grades summarize evidence quality, not whether a compound is appropriate, legal, or risk-free.

At a glance

What it is: O-304 / Pan-AMPK Activator + Mitochondrial Uncoupler — Oral Small Molecule — Pan-AMPK Activator, Small Molecule, Mitochondrial Uncoupler.
Why people use it: Used primarily for weight loss and mitochondrial health.

If you only read one thing

ATX-304 sits in an unusual position among all the compounds in this reference: it has the most scientifically rigorous development pathway (Phase 1 safety + Phase 2a DBRCT with positive results + active Phase 1b), the most institutional backing ($33.25M Series A from RA Capital and Future Ventures), and the most sophisticated mechanistic rationale (pan-AMPK activation + mitochondrial uncoupling). It is also being sold online as a research chemical at community doses of 100-300 mg/day — far below the 1,000 mg/day used in the clinical trial — and marketed as 'exercise in a pill,' 'the best longevity compound nobody's talking about,' and a GLP-1 alternative. The pharmaceutical development program is for patients with T2D, obesity, and metabolic disease. The community is primarily self-administering it for healthy adult fat loss, longevity optimization, and general metabolic enhancement — applications where ATX-304 has no controlled human trial data. The compound deserves both its excitement and its epistemic humility.

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Published literature

1human RCT0human studies6animal3in vitro

Human controlled evidence is the 28-day TELLUS Phase 2a oral O-304/ATX-304 trial in T2D on metformin; obesity and GLP-1-combination claims remain preclinical.

Evidence reality check

Human evidence

1 human study

1 randomized; 0 observational.

Preclinical base

9 lab signals

6 animal; 3 in-vitro/mechanistic.

Risk posture

No major flags listed

Review route-specific cautions before use.

Categories

Weight Loss & Metabolic Mitochondrial & Energy

Properties

Active malignancy: caution✓ Human RCTNot injectable

Evidence

CAnimal replicated

a small molecule

ATX-304 is an oral small molecule synthetic drug — not a protein, not a hormone. It is included in this reference because of its widespread use alongside peptides in the community's metabolic and longevity protocol space, and because it represents one of the most pharmacologically sophisticated small molecules the community has adopted in advance of its pharmaceutical approval. Chemical: a halogenated organic compound with two chlorine substituents. Peripherally restricted (minimal CNS penetration — by design). Oral bioavailability: well-characterized from clinical trials. Not injectable.

The AMPK Target — Why It Matters

AMPK (AMP-activated protein kinase) is often called the master regulator of cellular energy homeostasis. When the AMP:ATP ratio rises (signaling low energy — as in exercise, fasting, hypoxia), AMPK is activated by phosphorylation at Threonine 172. Active AMPK: inhibits anabolic processes (de novo lipogenesis via ACC phosphorylation; cholesterol synthesis via HMGCR phosphorylation; protein synthesis via mTOR inhibition); activates catabolic processes (fatty acid oxidation; glucose uptake in muscle via GLUT4 translocation; mitochondrial biogenesis via PGC-1α). ATX-304 activates AMPK by suppressing the dephosphorylation of Thr172 — keeping AMPK active without requiring cellular energy deficit. This mimics the AMPK signaling of exercise and caloric restriction without actually requiring either.

The Dual Mechanism — AMPK + Mitochondrial Uncoupling

ATX-304 has two distinct mechanisms. AMPK activation: as described above; the primary signaling mechanism; suppresses de novo lipogenesis and cholesterol synthesis; promotes glucose uptake and fatty acid oxidation; improves insulin sensitivity; cardiovascular and metabolic benefits. Mitochondrial uncoupling: independently of AMPK, ATX-304 increases basal oxygen consumption rate in cells; uncoupling means some of the proton gradient across the inner mitochondrial membrane is dissipated as heat rather than used to synthesize ATP; this creates an 'energy demand' that drives increased fat and glucose oxidation. The dual mechanism — signaling activation (AMPK) + hardware optimization (mitochondrial uncoupling) — distinguishes ATX-304 from compounds that only do one.

TELLUS Phase 2a — The Key Human Data

TELLUS (2016-2017): 28-day randomized, double-blind, placebo-controlled Phase 2a trial; 65 T2D patients stably on metformin; O-304 (ATX-304) 1,000 mg/day vs placebo. Primary analysis: fasting plasma glucose (FPG) reduction. In the predefined analysis population (FPG >7 to <13.3 mmol/L at Day 1): O-304 group mean FPG reduction = -0.60 mM; placebo group = -0.10 mM; p = 0.0096. Microvascular perfusion in calf muscle (by MRI): improved with O-304. Safety: well-tolerated; no significant adverse effects. The post-hoc nature of the FPG subgroup analysis is a limitation. Grade B — DBRCT; clinically meaningful effect; post-hoc subgroup caveat.

Clinical Development Status (2025-2026)

Phase 1 (Betagenon): completed; safety established in young healthy subjects, overweight middle-aged subjects, and T2D patients on metformin. Phase 2a TELLUS (Betagenon): completed 2017; positive FPG and microvascular perfusion data. Phase 1b (Amplifier Therapeutics): first patient dosed ~2023-2024; $33.25 million Series A (RA Capital, Future Ventures); currently enrolling. ENDO 2025 (July 2025): preclinical DIO mouse data presented showing ATX-304 monotherapy and ATX-304 + semaglutide combination body weight and composition effects; ATX-304 after semaglutide withdrawal data. Phase 2 obesity: planned/ongoing as of 2026. FDA/EMA approval: not yet.

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