SS-31
| Category | Other Peptides |
| Goals | Longevity & Anti-Aging |
| Evidence level | Clinical (approved for one rare disease; investigational elsewhere) |
| Legal status | FDA-approved for Barth syndrome (FORZINITY, Sep 2025); otherwise investigational |
| FDA status | Approved (Barth syndrome) 2025-09-19; all other indications investigational |
| Half-life | ~ a few hours after subcutaneous dosing (clinical PK) |
| Routes | Subcutaneous · Intravenous |
| CAS / MW / Sequence | 736992-21-5 · 639.8 g/mol · D-Arg-Dmt-Lys-Phe-NH₂ (4 aa) |
| Last reviewed | 2026-06-07 |
In one line
A mitochondria-targeting tetrapeptide (elamipretide) that binds cardiolipin in the inner mitochondrial membrane; now FDA-approved for Barth syndrome and in trials for other mitochondrial diseases.
Evidence at a glance
SS-31 has the strongest clinical pedigree of the peptides on this wiki — including a 2025 FDA approval for the ultra-rare Barth syndrome. But that approval is narrow and accelerated (confirmatory trial pending), and the popular longevity/anti-aging uses are not approved and largely unproven in humans. See Evidence Grading Explained and the Disclaimer.
Key Takeaways
- A synthetic cell-permeable tetrapeptide (D-Arg-Dmt-Lys-Phe-NH₂) that concentrates in mitochondria and binds cardiolipin.
- Stabilizes mitochondrial cristae, reduces oxidative stress, and supports ATP production.
- FDA-approved in September 2025 as FORZINITY (Stealth BioTherapeutics) for Barth syndrome in patients ≥30 kg — the first mitochondria-targeted therapy ever approved.
- Has been studied in many trials (heart failure, mitochondrial myopathy, dry AMD); results have been mixed, and most non-Barth indications remain investigational.
- Popular longevity use far outruns the human evidence for that purpose.
What Is It
SS-31 (international nonproprietary name elamipretide; development codes MTP-131 / Bendavia; brand FORZINITY) is a synthetic mitochondria-targeting tetrapeptide. Its alternating aromatic/cationic design — including the unusual residue 2’,6’-dimethyltyrosine (Dmt) — lets it cross membranes and accumulate in the inner mitochondrial membrane without depending on membrane potential. Unlike most peptides on this wiki, it has been through formal clinical development and now has a regulatory approval for one indication.
Mechanism of Action
Mechanism is supported by cell, animal, and clinical work:
- Cardiolipin binding (established) — selectively associates with cardiolipin, a phospholipid unique to the inner mitochondrial membrane, stabilizing cristae architecture.
- Improved electron transport / ATP (preclinical–clinical) — better-organized cristae support respiratory-chain efficiency and ATP synthesis.
- Reduced oxidative stress (preclinical) — limits reactive-oxygen-species generation and lipid peroxidation.
- Mitophagy / morphology normalization (preclinical) — improves mitochondrial morphology and quality control in disease models (e.g. Barth syndrome).
Limitations
The Barth approval rests on a muscle-strength endpoint in a small open-label dataset under accelerated approval; benefit must be confirmed. Several large trials in other diseases did not meet primary endpoints.
Evidence by Outcome
| Outcome | Evidence | Notes |
|---|---|---|
| Barth syndrome (muscle strength) | Approved | FDA accelerated approval 2025; confirmatory trial pending |
| Mitochondrial myopathy | Clinical | Trials (e.g. MMPOWER-3) — mixed/negative primary endpoints |
| Heart failure | Clinical | Trials (e.g. PROGRESS-HF) — not established |
| Dry AMD / retinal disease | Clinical | ReCLAIM and related — investigational |
| General anti-aging / longevity | Anecdotal | Popular off-label rationale; no approval, minimal human data |
Reported Dosing
Not medical advice
The only approved dosing is the FORZINITY label for Barth syndrome, prescribed and supervised by a clinician. Community/off-label protocols below are reported, not validated. See Reconstitution & Dosing Math and Injection Technique.
| Route | Dose (reported / studied) | Frequency | Context |
|---|---|---|---|
| Subcutaneous | 40 mg/day used in several trials | Daily | Approved label (Barth) defines its own dosing |
| Subcutaneous (community) | ~5–10 mg/day reported | Daily | Off-label longevity use; unvalidated |
| Intravenous | Used in some hospital-based trials | Per protocol | Investigational |
Pharmacokinetics
Clinical PK supports roughly once-daily subcutaneous dosing, with a circulating half-life on the order of a few hours (indication- and dose-dependent). It distributes to and concentrates within mitochondria. See Half-Life & Pharmacokinetics.
Side Effects & Risks
- In trials the most common adverse effect was injection-site reactions (redness, itching, pain).
- Headache, nausea, and other generally mild events have been reported.
- Because non-Barth uses are investigational, the long-term safety of off-label longevity dosing is not established.
- For the approved product, follow the FDA label and prescriber guidance.
- Sourcing risk: “research chemical” SS-31 is not the regulated product — identity/purity vary; see Sourcing and Red Flags & Scams.
- See Side Effects & Risk Management.
Cycling
There is no evidence-based cycling protocol for off-label/longevity use. Approved use follows continuous clinician-directed dosing per label. See Cycling.
Stacks It Appears In
- Longevity/mitochondrial stacks discussed alongside NAD+ and MOTS-c (community use; no clinical validation as a stack).
Comparisons
- vs MOTS-c — SS-31 physically stabilizes the mitochondrial membrane (cardiolipin); MOTS-c is an AMPK-activating metabolic signal.
- vs NAD+ — both are pitched for “mitochondrial/energy” support, but SS-31 is a targeted peptide with a drug approval, while NAD+ is a coenzyme/supplement.
Sourcing & Quality
The approved product (FORZINITY) is a regulated prescription drug. Material sold as “SS-31 research chemical” is not that product and carries the usual identity/purity uncertainty: How to Read a CoA, Sourcing, Red Flags & Scams. Reconstitution and storage: Reconstitution & Dosing Math, Storage & Handling. No vendors are endorsed here.
Legal & Regulatory Status
(As of 2026-06-07.) On 2025-09-19 the FDA granted accelerated approval to elamipretide HCl (FORZINITY, Stealth BioTherapeutics; NDA 215244) for Barth syndrome — specifically to improve muscle strength in adult and pediatric patients weighing ≥30 kg — the first FDA-approved mitochondria-targeted therapy. Continued approval may depend on a confirmatory trial. All other uses (including longevity) remain investigational/off-label. Research-chemical SS-31 is not an approved drug. See Regulatory & Legal Status.
FAQ
Is SS-31 FDA-approved? Yes — but only as FORZINITY for Barth syndrome (accelerated approval, Sep 2025). Every other use is investigational.
Does it work for anti-aging? There is no human evidence that SS-31 extends lifespan or reverses aging. That use is off-label and unproven.
Why did some big trials “fail”? Several large trials (heart failure, mitochondrial myopathy) did not meet their primary endpoints, which is why the approved indication is narrow.
Is “research-chemical SS-31” the same as the approved drug? No. The approved drug is a regulated, tested product; research-chemical material is unregulated and of uncertain quality.
References
- U.S. FDA (2025). “FDA Grants Accelerated Approval to First Treatment for Barth Syndrome.” fda.gov
- Stealth BioTherapeutics (2025-09-19). FORZINITY (elamipretide HCl) accelerated-approval announcement.
- “Elamipretide: A Review of Its Structure, Mechanism of Action, and Therapeutic Potential.” Int. J. Mol. Sci. (2025). MDPI
- “Mitochondrial protein interaction landscape of SS-31.” PMC (2020). PMC7334473
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