Both are linked to mitochondria, but SS-31 is a synthetic tetrapeptide with an FDA accelerated approval, while MOTS-c has no approved use or completed trial.
By the MOTS-C Peptide editorial team·Last reviewed ·Sources: editorially approved
Short answer
These two are often discussed together because both involve mitochondria, but they have little else in common. SS-31 (elamipretide) is a synthetic four-residue peptide that received FDA accelerated approval in September 2025 for Barth syndrome, a rare genetic disease [FDA 2025]. MOTS-c is a natural 16-residue peptide with no approved use and no completed trial [FDA 2026].
MOTS-c and SS-31 (elamipretide) compared field by field. Each column describes that substance only; the rows are not scores.
MOTS-c
SS-31 (elamipretide)
What it is
A natural 16-amino-acid peptide
A synthetic 4-residue peptide, D-Arg-Dmt-Lys-Phe-NH₂
Origin
Encoded in mitochondrial DNA (MT-RNR1)
Designed in a laboratory; contains a D-amino acid and 2,6-dimethyltyrosine, so no gene encodes it
Molecular weight
2174.6 g/mol
639.8 g/mol
Proposed target
Unidentified
Cardiolipin, a lipid of the inner mitochondrial membrane
Approval status
Not approved for any use
FDA accelerated approval, September 2025, as Forzinity for Barth syndrome
Completed human trials
None published
Yes, including the randomised TAZPOWER trial and its open-label extension
Evidence the approval rested on
n/a
Knee extensor muscle strength, an intermediate endpoint, with a confirmatory trial required
Prohibited in sport
Yes, at all times (WADA S4)
Not listed by name on the WADA Prohibited List
One is a drug, the other is not
This is the difference that matters, and it is not a difference of degree. Elamipretide went through the regulatory process: registered trials, a submitted application, FDA review and an approval with an indication attached [FDA 2025]. The randomised TAZPOWER trial and its 168-week open-label extension are published [Thompson 2024].
MOTS-c has none of that. One Phase 2a trial is recruiting, with completion estimated for 2028 [NCT07505745], and FDA’s 2026 review found no human data on MOTS-c by any route [FDA 2026]. The two sit at opposite ends of the development path.
Chemistry sets them apart more than the shared label suggests
“Mitochondrial peptide” covers both, which flatters the resemblance. Elamipretide is four residues and 639.8 g/mol, built with a D-amino acid and a modified tyrosine [PubChem]; those modifications are deliberate design choices that no natural translation would produce. MOTS-c is 16 residues and 2174.6 g/mol, read from a sequence in mitochondrial DNA [UniProt 2026][PubChem].
Their proposed mechanisms do not overlap either. Elamipretide is described as binding cardiolipin in the inner mitochondrial membrane, a defined molecular interaction. For MOTS-c, FDA stated that the molecular targets through which it acts remain unknown [FDA 2026]. Having a known target is a prerequisite for the kind of development elamipretide completed.
Anti-doping status differs
MOTS-c is named on the WADA Prohibited List under S4 as an example of an AMPK activator, prohibited at all times [WADA 2026]. Elamipretide is not listed by name. Athletes should check the list edition in force rather than relying on this page; see regulatory status.
How to read material that pairs them
Content that presents these as alternatives usually borrows elamipretide’s regulatory credibility for MOTS-c. The approval belongs to one molecule, for one rare disease, on one endpoint. Of the 253 publications indexed here, none mentions elamipretide. See MOTS-c vs humanin for a comparison that does have overlapping research behind it.
Frequently asked questions
What is the difference between MOTS-c and SS-31?
MOTS-c is a 16-amino-acid peptide your mitochondria encode naturally. SS-31, also called elamipretide, is a synthetic four-residue peptide designed in a laboratory; it contains a D-amino acid and a modified tyrosine, so no gene encodes it. They are related only by both being studied in connection with mitochondria.
Is SS-31 FDA approved?
Elamipretide received FDA accelerated approval in September 2025 as Forzinity, for improving muscle strength in Barth syndrome in patients weighing at least 30 kg. That is a narrow indication in an ultra-rare genetic disease, granted on an intermediate endpoint, with a confirmatory trial required.
Is MOTS-c FDA approved?
No. MOTS-c is not approved for anything, and in 2026 FDA staff recommended against adding it to the list of substances pharmacies may compound.
Has any study compared MOTS-c and SS-31?
Not in this index. None of the indexed MOTS-c publications mentions SS-31 or elamipretide. Any ranking of one against the other is inference.
Do they work the same way?
No proposed mechanism is shared. SS-31 is described as binding cardiolipin, a lipid of the inner mitochondrial membrane. MOTS-c has no identified binding target at all.
National Center for Biotechnology Information. PubChem Compound CID 146675088: Mots-c. Source[retrieved 2026-11-11]
National Center for Biotechnology Information. PubChem Compound CID 11764719: Elamipretide (SS-31). Source[retrieved 2026-11-11]
U.S. Food and Drug Administration (2025-09-19). FDA Grants Accelerated Approval to First Treatment for Barth Syndrome. Source[retrieved 2026-11-11]
Thompson WR et al., Genet Med (2024-07). Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER. Source[retrieved 2026-11-11]
U.S. Food and Drug Administration (2026-05-11). FDA Briefing Document: MOTS-c-Related Bulk Drug Substances (MOTS-c (free base) and MOTS-c acetate). Source[retrieved 2026-11-11]
ClinicalTrials.gov (2026-04-01). MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity (NCT07505745). Source[retrieved 2026-11-11]
World Anti-Doping Agency (2026-01-01). The Prohibited List (S4 Hormone and Metabolic Modulators: activators of AMP-activated protein kinase). Source[retrieved 2026-11-11]