Comparison
MOTS-c vs Rapamycin
Side-by-side of MOTS-c and Rapamycin. 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.
Rapamycin
Rapamycin for longevity: sirolimus, an mTOR inhibitor with ITP mouse lifespan data. Off-label geroprotective dosing remains investigational.
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
Rapamycin
- •Inhibits mTORC1 signaling by binding FKBP12, reducing protein synthesis and relieving autophagy suppression
- •ITP mouse program reproduced lifespan extension of ~10 to 25% across multiple genetic backgrounds and sexes
- •Mannick trials showed improved influenza vaccine response in elderly adults using analogs of rapamycin
- •PEARL human trial reported acceptable safety at 5 to 10 mg weekly with some functional and lean-mass signals
- •Common dose-limiting adverse effects include stomatitis, acne-like rash, and mildly elevated lipid markers
- •CYP3A4 substrate: grapefruit, ketoconazole, and clarithromycin substantially raise rapamycin exposure
Side-by-side
| Attribute | MOTS-c | Rapamycin |
|---|---|---|
| Category | peptide | pharmaceutical |
| Also known as | Mitochondrial Open Reading Frame of the Twelve S rRNA-c, MOTSc | Sirolimus, Rapamune |
| Half-life (hr) ↗ | 0.5 | 62 |
| Typical dose (mg) ↗ | 5 | 6 |
| Dosing frequency | 2-3x weekly | weekly (longevity protocols); daily for transplant indication |
| Routes | subcutaneous | oral |
| Onset (hr) | 1 | 1 |
| Peak (hr) | 4 | 2 |
| Molecular weight | 1880.18 | 914.17 |
| Molecular formula | C82H132N22O25S2 | C51H79NO13 |
| 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. | Binds FKBP12, and the resulting complex inhibits mTORC1, reducing protein synthesis and autophagy suppression downstream of nutrient and growth-factor signaling. |
| Legal status | Not FDA approved; research-use-only grey market; not currently on WADA Prohibited List | Prescription only (off-label for longevity) |
| WADA status | unknown | allowed |
| DEA / Rx | Not scheduled (research chemical) | Rx only (not a controlled substance) |
| Pregnancy | Insufficient data; not recommended | Not recommended |
| CAS | 1627580-64-6 | 53123-88-9 |
| PubChem CID | 139599184 | 5284616 |
| Wikidata | Q24832108 | Q410174 |
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)
Rapamycin
Common side effects
- mouth ulcers (stomatitis)
- acne-like rash
- GI upset
- altered lipid panel
- delayed wound healing
Contraindications
- active infection
- severe hepatic impairment
- planned surgery (delayed wound healing)
- pregnancy
- live vaccines within dosing window
Interactions
- strong CYP3A4 inhibitors (ketoconazole, clarithromycin, grapefruit): substantially raises rapamycin levels, toxicity risk(major)
- strong CYP3A4 inducers (rifampin, St John's wort): lowers rapamycin levels, reduced effect(major)
- ACE inhibitors: increased risk of angioedema(moderate)
- live vaccines: reduced vaccine efficacy due to immunosuppression(major)
Which Should You Take?
Rapamycin comes out ahead for most readers on the criteria we weight: 2 catalogued goals, prescription-only, oral dosing, with a Tier-A outcome catalogued. MOTS-c is the right call when one of the conditionals below applies.
- → If your priority is metabolic health and glucose control, pick MOTS-c.
- → If your priority is mitochondrial function, pick MOTS-c.
- → If your priority is immune support, pick Rapamycin.
Edge case: If you cannot self-administer injections, Rapamycin is the only oral option in this pair.
Default choice: Rapamycin. Wider use case, a Tier-A evidence outcome catalogued, and broader goal coverage. Reach for MOTS-c only if your priority sits squarely in the goals it owns 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 Rapamycin?
MOTS-c and Rapamycin differ in category (peptide vs pharmaceutical), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, MOTS-c or Rapamycin?
MOTS-c half-life is 0.5 hours; Rapamycin half-life is 62 hours.
Can you stack MOTS-c with Rapamycin?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
Go deeper