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Professor Peptides
Research compound

O-304

Also known as O-304 · O304 · pan-AMPK activator O304

Pan-AMPK activator described as an exercise mimetic; reported tolerated in humans

Last reviewed · Educational reference — not medical advice.

Formula
C16H11Cl2N3O2S
Molecular weight
380.2 g/mol
Half-life
Not characterised in published human pharmacokinetic studies
Route
Oral in the published work
CAS
1261289-04-6
PubChem
50923806 (opens in new tab)
Status
Clinical-stage small molecule — reported well tolerated in humans
Mechanism
Direct pan-AMPK activator. AMPK is the cellular energy sensor activated by falling energy charge; pharmacological activation shifts metabolism toward fuel oxidation and insulin sensitisation, reproducing part of the signalling produced by exercise.
01

Overview

O-304 is a direct pan-AMPK activator developed as an exercise mimetic. Like 5-Amino-1MQ it is sold alongside peptides but is not one — it is a small molecule (4-chloro-N-(2-(4-chlorobenzyl)-3-oxo-2,3-dihydro-1,2,4-thiadiazol-5-yl)benzamide, C16H11Cl2N3O2S, MW 380.2).

AMP-activated protein kinase is the cell's energy sensor: it is activated when cellular energy charge falls, as during exercise, and switches metabolism toward fuel oxidation. "Pan" activation means the compound is not selective for a single AMPK isoform combination, which is the pharmacological pitch — broader activation, closer to the physiological signal.

The most substantial published study used aged mice. O-304 both prevented and reversed age-associated hyperinsulinaemia and insulin resistance, and improved cardiac function and exercise capacity. The authors positioned this as preclinical evidence that the compound mimics benefits of exercise for individuals unable to exercise regularly.

One point genuinely distinguishes O-304 from most compounds in this catalogue: the authors describe it as

already well tolerated in humans and in clinical development. That is a stronger safety position than the typical research chemical — though tolerability is not efficacy, and no published trial demonstrates a clinical outcome in people.

Research areasAMPK activationExercise mimeticsInsulin resistance and ageingCardiac functionMetabolic dysfunction
02

What the evidence shows

Separated by study type
HumanClinical trials and human studies
Described by the investigators as well tolerated in humans and in clinical development. No published trial reporting a clinical efficacy outcome was located.
AnimalRodent and other animal models
In aged mice, O-304 prevented and reversed age-associated hyperinsulinaemia and insulin resistance, and improved cardiac function and exercise capacity.
In vitroCell and tissue studies
Direct pan-AMPK activation is the established biochemical activity.
03

Key studies & findings

1 study
  1. 1

    In aged mice, the pan-AMPK activator O304 prevented and reverted age-associated hyperinsulinaemia and insulin resistance, and improved cardiac function and exercise capacity — presented as preclinical evidence for an exercise-mimetic effect.

    Preclinical2021Communications Biology, 2021 (opens in new tab)

04

Benefits & effects

4 documented

  • Reversed age-associated insulin resistance in aged mice

    PreclinicalVerified

  • Improved cardiac function in aged mice

    PreclinicalVerified

  • Improved exercise capacity in aged mice

    PreclinicalVerified

  • Reported well tolerated in humans by the investigators

    Verified
05

Side effects & safety

1 reported

Safety noteResearch compound for laboratory use only. Not approved for human use; no established human safety database outside the trials cited here.

Recorded in the cited literature No published human adverse-event profile located.

  • Long-term consequences of chronic systemic AMPK activation uncharacterised

    unknown
06

Limitations & open questions

The efficacy evidence is entirely in aged mice. Human tolerability is asserted by the investigators, but no published human trial demonstrating metabolic or cardiac benefit was located. Indexed literature on this compound is very thin — a PubMed search returns only a handful of records. Chronic systemic AMPK activation has plausible off-target consequences in tissues where suppressing anabolic signalling is undesirable, and these have not been characterised in long-term human use.

07

Pharmacology

O-304 is 4-chloro-N-(2-(4-chlorobenzyl)-3-oxo-2,3-dihydro-1,2,4-thiadiazol-5-yl)benzamide (C16H11Cl2N3O2S, MW 380.2, CAS 1261289-04-6, PubChem CID 50923806). It is orally administered in the published work. Detailed human pharmacokinetic parameters have not been published in the sources located.

08

Frequently asked questions

Is O-304 a peptide?

No. It is a small-molecule thiadiazole benzamide, C16H11Cl2N3O2S. It is sold on peptide sites but has no amino acid sequence.

What does 'exercise mimetic' mean here?

AMPK is one of the signals exercise produces inside cells. Activating it pharmacologically reproduces part of that signalling. In aged mice this improved insulin sensitivity, cardiac function and exercise capacity. It does not reproduce everything exercise does.

Is O-304 safe in humans?

The investigators state it is well tolerated in humans and in clinical development. Tolerability data are not the same as demonstrated efficacy or long-term safety, and no published human outcome trial was located.

09

Citations

1 sources
  1. 1
    AMPK activator O304 improves metabolic and cardiac function, and exercise capacity in aged mice (opens in new tab)Ericsson M, Steneberg P, Nyrén R, Edlund H (2021) · doi:10.1038/s42003-021-02837-0