Comparison
MOTS-c vs Semax
Side-by-side of MOTS-c and Semax. Every row below is pulled from the compound schema and will update as our data grows. For deeper reads, follow through to each compound page.
MOTS-c
MOTS-c peptide is a 16-amino-acid mitochondrial-derived peptide. Preclinical signals for insulin sensitivity, exercise capacity, dosage notes.
Semax
Semax peptide benefits: nootropic ACTH(4-10) analog without corticotropic activity. Cognitive enhancement, neuroprotection, intranasal dosing, Russian stroke.
Effects at a glance
MOTS-c
- •16-amino-acid peptide encoded in mitochondrial DNA (12S rRNA region); discovered 2015
- •Activates AMPK in skeletal muscle and liver; improves insulin sensitivity in rodent models
- •Circulating endogenous levels decline with age, motivating the longevity-restoration hypothesis
- •CohBar's MOTS-c analog CB4211 discontinued after phase 1b NASH readout did not meet endpoints
- •Anecdotal protocols use 5 to 10 mg subcutaneously 2 to 3 times weekly
- •Not on the WADA Prohibited List as of 2026; future scrutiny likely given exercise-mimetic mechanism
Semax
- •Synthetic heptapeptide analog of ACTH(4-10) developed in Russia in the 1980s
- •Approved in Russia for ischemic stroke, cognitive impairment, and cerebrovascular disorders
- •Lacks the corticotropic activity of native ACTH due to the Pro-Gly-Pro stabilizing tail
- •Russian RCTs report improved cognitive recovery in acute ischemic stroke versus standard care
- •Modulates BDNF and NGF expression and dopaminergic signaling in preclinical models
- •Standard route is intranasal; not FDA approved; research-use-only outside Russia
Side-by-side
| Attribute | MOTS-c | Semax |
|---|---|---|
| Category | peptide | peptide |
| Also known as | Mitochondrial Open Reading Frame of the Twelve S rRNA-c, MOTSc | Met-Glu-His-Phe-Pro-Gly-Pro, ACTH(4-10) Pro-Gly-Pro analog |
| Half-life (hr) ↗ | 0.5 | 0.5 |
| Typical dose (mg) ↗ | 5 | 0.6 |
| Dosing frequency | 2-3x weekly | 2-3x daily (intranasal) |
| Routes | subcutaneous | intranasal |
| Onset (hr) | 1 | 0.5 |
| Peak (hr) | 4 | 2 |
| Molecular weight | 1880.18 | 813.94 |
| Molecular formula | C82H132N22O25S2 | C37H51N9O10S |
| Mechanism | Mitochondrial-derived peptide that activates AMPK in skeletal muscle and liver, improves insulin sensitivity, and translocates to the nucleus under metabolic stress to modulate nuclear gene expression in retrograde mitochondrial signaling. | Modulates BDNF and NGF expression in hippocampus and cortex, enhances dopaminergic and serotonergic signaling, and reduces oxidative stress markers in preclinical ischemia models. Lacks corticotropic activity of native ACTH. |
| Legal status | Not FDA approved; research-use-only grey market; not currently on WADA Prohibited List | Approved in Russia for stroke and cognitive disorders; not FDA approved; research-use-only grey market elsewhere |
| WADA status | unknown | unknown |
| DEA / Rx | Not scheduled (research chemical) | Not FDA approved; not scheduled; research-chemical status outside Russia |
| Pregnancy | Insufficient data; not recommended | Not recommended; insufficient data |
| CAS | 1627580-64-6 | 80714-61-0 |
| PubChem CID | 139599184 | 9811102 |
| Wikidata | Q24832108 | Q4413083 |
Safety profile
MOTS-c
Common side effects
- injection-site irritation
- transient fatigue
- headache (anecdotal)
Contraindications
- pregnancy
- lactation
- active malignancy (theoretical)
- severe hypoglycemia risk on concurrent insulin or sulfonylurea
Interactions
- insulin: additive insulin sensitization may increase hypoglycemia risk(moderate)
- metformin: both activate AMPK; theoretical additive metabolic effect, no controlled data(minor)
- sulfonylureas: increased hypoglycemia risk via additive insulin sensitization(moderate)
Semax
Common side effects
- mild nasal irritation
- transient mild headache
- rare mild euphoria or activation
Contraindications
- pregnancy
- lactation
- acute psychotic disorder
- severe hypertension (caution due to mild activating effect)
Interactions
- stimulants (caffeine, amphetamines): potential additive activation; monitor for overstimulation(minor)
- antipsychotics: theoretical antagonism via dopaminergic modulation(minor)
Which Should You Take?
MOTS-c and Semax score evenly on the criteria we weight (goal breadth, legal accessibility, evidence depth). The conditionals below should drive the decision more than any aggregate score.
- → If your priority is healthspan extension, pick MOTS-c.
- → If your priority is metabolic health and glucose control, pick MOTS-c.
- → If your priority is focus or working memory, pick Semax.
- → If your priority is long-term neuroprotection, pick Semax.
Default choice: either is defensible. MOTS-c edges out on goal breadth + legal accessibility; Semax is the right call if your priority sits in the goals listed above.
This verdict is generated from each compound's schema (goals, legal status, evidence outcomes, dosing route). It updates automatically as our compound data evolves; the deeper read sits on each individual compound page.
Common questions
What is the difference between MOTS-c and Semax?
MOTS-c and Semax differ in category (peptide vs peptide), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, MOTS-c or Semax?
MOTS-c half-life is 0.5 hours; Semax half-life is 0.5 hours.
Can you stack MOTS-c with Semax?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
Go deeper