AICAR vs MOTS-c
AICAR (AMPK activator (small molecule)) and MOTS-c (Mitochondrial-derived peptide) are documented as co-studied in the PeptiDex library. This page puts the two entries side by side on class, molecular weight, half-life, origin, mechanism and studied research areas — every value taken from the entry it belongs to.
Why these two are co-studied
Cross-referenced for research context — not a usage or combination recommendation.
At a glance
| Attribute | AICAR | MOTS-c |
|---|---|---|
| Compound class | AMPK activator (small molecule) | Mitochondrial-derived peptide |
| Research category | Metabolic & Mitochondrial | Metabolic & Mitochondrial |
| Length (amino acids) | Not documented | 16 amino acids |
| Molecular weight | ~258 g/mol | ~2174 g/mol |
| Half-life | ~90 min (plasma, parent riboside); intracellular ZMP sustains AMPK activation for several hours | Not documented |
| Origin | AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide, also called acadesine) is a small-molecule nucleoside analog and an intermediate in de novo purine biosynthesis. It is not a peptide. | MOTS-c (Mitochondrial ORF of the 12S rRNA type-c) is a 16-amino-acid mitochondrial-derived peptide encoded within the MT-RNR1 (12S rRNA) region of mitochondrial DNA. It was described in 2015 and is one of a small family of mitochondrial-derived peptides. |
“Not documented” means the PeptiDex entry records no value for that field. Nothing on this page is estimated, and no figure is carried over from one compound to the other.
How AICAR works
Inside cells AICAR is phosphorylated to ZMP, an AMP analog that activates AMP-activated protein kinase (AMPK), a central sensor of cellular energy status. AMPK activation shifts metabolism toward catabolic, energy-generating pathways, including increased glucose uptake and fatty-acid oxidation. In preclinical studies AICAR has been used as a pharmacological AMPK activator and described as an exercise-mimetic.
How MOTS-c works
MOTS-c is reported to regulate metabolic homeostasis, in part via activation of the AMPK pathway and modulation of the folate-methionine cycle and de novo purine biosynthesis. It has been described to translocate to the nucleus under metabolic stress and influence stress-response gene expression. Preclinical work links it to improved insulin sensitivity and glucose uptake in skeletal muscle; it is also described as exercise-responsive.
Mechanistic descriptions reflect published research-literature understanding and are quoted from each compound's own entry. Much peptide research is preclinical (in-vitro or animal-model); mechanism in humans may differ and is not established for many compounds.
Where each one appears in the literature
The research contexts each entry documents. Listing a research area is not a claim of efficacy or a therapeutic indication, and the two lists are not scored against each other.
AICAR
MOTS-c
What sets each apart
AICAR
Unlike SLU-PP-332 (ERR-level) or the GH fragments, AICAR acts directly on the AMPK energy-sensing pathway as an AMP analog.
MOTS-c
Unlike the GH-derived fragments here, MOTS-c is endogenously encoded in the mitochondrial genome and acts as a broad metabolic regulator rather than a targeted lipolytic fragment.
Frequently asked questions
Is AICAR a peptide?
No. AICAR (5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, also called acadesine or AICA-riboside) is a small-molecule nucleoside, not a peptide. Its molecular formula is C9H14N4O5 (MW ~258.2, CAS 2627-69-2) and it has no amino-acid sequence.
What is the mechanism of AICAR?
Inside cells AICAR is phosphorylated to ZMP, an AMP mimetic that activates AMP-activated protein kinase (AMPK). AMPK activation shifts metabolism toward energy production, increasing glucose uptake and fatty-acid oxidation. Because AMPK is a key exercise-responsive energy sensor, AICAR is studied as an exercise-mimetic metabolic compound.
What is AICAR studied for?
AICAR is a widely-used research tool for AMPK biology and is studied in models of glucose metabolism, endurance/muscle physiology, mitophagy, and metabolic disease. It has also been examined in cardioprotection (acadesine). Its exercise-mimetic effects on endurance in rodents led to attention from anti-doping authorities.
What is MOTS-c and where does it come from?
MOTS-c (Mitochondrial Open-reading-frame of the Twelve-S rRNA type-c) is a 16-amino-acid mitochondrial-derived peptide (MDP) encoded within the 12S rRNA region of mitochondrial DNA, rather than by the nuclear genome. First described in 2015, it is studied as a regulator of metabolic homeostasis. Its sequence and MDP origin make it structurally distinct from most catalog peptides.
What is MOTS-c studied for?
MOTS-c is studied in models of metabolic homeostasis, insulin sensitivity, exercise capacity, and aging. Research reported that MOTS-c levels rise with exercise and that exogenous MOTS-c improved glucose tolerance, insulin sensitivity, and running endurance in aged mice. It is thought to act partly via AMPK-linked metabolic signaling.
How is MOTS-c thought to work mechanistically?
MOTS-c is reported to translocate to the nucleus under metabolic stress and influence adaptive gene-expression programs, and it engages the AMPK pathway and folate/one-carbon metabolism to promote glucose uptake and fatty-acid oxidation. This positions it as a signaling peptide linking mitochondrial state to whole-body metabolism in preclinical models.
Answers are the ones published on each compound's own PeptiDex entry. They are educational summaries of research-literature context and are not medical advice.