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Research use only
· 7 min read
Most research peptides chase a protein receptor; SS-31 (elamipretide) aims at a fat instead. Its reported molecular target is a phospholipid - cardiolipin, the anionic lipid that lives almost exclusively on the inner mitochondrial membrane - rather than a receptor in the conventional sense. That distinction shapes everything from the mechanism literature to the identifier records, and it is worth keeping in mind before reading either. Kovalabs supplies SS-31 strictly as a research reagent; everything below describes what published studies have investigated, not any human use.
| Compound | SS-31 (elamipretide) |
|---|---|
| Development code / synonyms | SS-31, MTP-131, elamipretide (INN) |
| Class / mechanism | Mitochondria-targeted cationic tetrapeptide; cardiolipin-associating inner-membrane peptide |
| Sequence | D-Arg-Dmt-Lys-Phe-NH2 (Dmt = 2,6-dimethyl-L-tyrosine) |
| Molecular formula | C32H49N9O5 |
| Molecular weight | 639.8 g/mol (free base) |
| CAS number | 736992-21-5 (free base) |
| PubChem CID | 11764719 |
| Other identifiers | UNII 87GWG91S09; ChEMBL CHEMBL3833370; ChEBI 233331; InChIKey SFVLTCAESLKEHH-WKAQUBQDSA-N |
SS-31 is the Szeto-Schiller peptide 31, named for its co-developers and indexed under the recommended INN elamipretide. The sequence is D-Arg-2,6-dimethyl-Tyr(Dmt)-Lys-Phe-NH2: four residues, C-terminally amidated, with alternating cationic positions (D-arginine and lysine) and aromatic positions (dimethyltyrosine and phenylalanine) giving the molecule its amphipathic character. The dimethyl substitution on the tyrosine ring is a deliberate structural feature that distinguishes it from standard tyrosine and is part of the pharmacophore description in the primary literature.
The identifiers are clean but carry one trap worth flagging. The free-base record is PubChem CID 11764719, CAS 736992-21-5, molecular formula C32H49N9O5, molecular weight 639.8 g/mol - cross-checked via four independent PubChem routes (name lookup, reverse SS-31 lookup, CAS cross-reference, and synonyms list), all resolving to the same record. The synonyms include elamipretide, SS-31, MTP-131, UNII 87GWG91S09, ChEMBL CHEMBL3833370, and the sequence string itself. The trap: CAS 1334953-95-5 is the acetate salt (elamipretide acetate / MTP-131 acetate), a separate registry entry for a different physical form. The two should not be conflated. A stray entry in the PubChem synonyms field also describes the molecule as a five-amino-acid peptide; every primary source treats SS-31 as a four-residue tetrapeptide, and that synonym appears to be a labelling artefact rather than a structural variant. Branded trade names of separate investigational or licensed medicinal products are not applicable to this research-grade material and are not listed here. For the product specification and batch documentation, see the SS-31 product page and our certificates of analysis.
| Property | Detail |
|---|---|
| Peptide length | Tetrapeptide (4 residues) |
| Sequence | D-Arg-Dmt-Lys-Phe-NH2 |
| Structural character | Amphipathic; alternating cationic and aromatic residues |
| Reported molecular target | Cardiolipin (anionic inner-mitochondrial-membrane phospholipid) |
| Reported localisation | Inner mitochondrial membrane (electrostatic partitioning context) |
| Free-base CAS | 736992-21-5 |
| Acetate-salt CAS (kept separate) | 1334953-95-5 (elamipretide acetate / MTP-131 acetate, not the free base) |
| PubChem CID | 11764719 |
The mechanistic picture for SS-31 has been built up through biophysics rather than classical receptor pharmacology, which makes the literature read differently from most peptide mechanism sections. The central claim - electrostatic partitioning into the inner mitochondrial membrane via cardiolipin association - rests on a series of in-vitro and computational studies, each characterising a distinct physical feature of the interaction.
Birk and colleagues (J Am Soc Nephrol 2013, PMID 23813215) used a polarity-sensitive fluorescent analogue of SS-31 to characterise its binding to cardiolipin in vitro, and examined the SS-31/cardiolipin association in relation to cytochrome c peroxidase activity. That work grounded the cardiolipin-binding description in direct biophysical measurement rather than inference from localisation data alone.
Mitchell, Alder and colleagues (J Biol Chem 2020, PMID 32273339) examined the membrane biophysics in more detail. They reported that SS-31 partitions into the membrane interfacial region with an affinity and lipid-binding density related to membrane surface charge, and that it modulates the surface electrostatics of both model and mitochondrial membranes. Reported endpoints in that in-vitro and molecular-dynamics study included lipid packing and divalent-cation (calcium) distribution at the interface - a level of physical detail that is useful for assessing how the molecule interacts with membrane architecture rather than with a single protein target.
The same group followed up with an NMR and molecular-dynamics study (eLife 2022, PMID 35913044) producing the first structural models for this class of mitochondria-targeted tetrapeptides. Analogues bound cardiolipin-containing membranes and differed in equilibrium binding behaviour and effect on membrane surface charge - providing a structural basis for comparing members of the SS-peptide series rather than treating them as equivalent.
Separately, Chavez, Bruce and colleagues (PNAS 2020, PMID 32554501) used chemical cross-linking with mass spectrometry to map the mitochondrial protein interactors of SS-31. The interactors identified were all known cardiolipin binders, falling into oxidative-phosphorylation and 2-oxoglutarate-metabolism groups, with cross-linked residues often proximal to cardiolipin-protein interaction regions. That proteomics approach adds a dimension the membrane-biophysics studies cannot: it identifies which specific proteins sit within cross-linking distance of SS-31 at the inner membrane.
A mechanism-of-action review by Szeto (Br J Pharmacol 2014, PMID 24117165) describes the peptide as partitioning selectively to the inner mitochondrial membrane through electrostatic attraction of its cationic residues and cardiolipin association, and sets out the background role of cardiolipin in cristae formation, in organising respiratory complexes, and in the cardiolipin-cytochrome c interaction. The relative membrane partitioning of the peptide is characterised within that review. These are mechanism and study-design descriptions only; no clinical effect or benefit is asserted. For related mitochondrial-research reagents, see the cellular research category and the MOTS-c research page.
SS-31 has accumulated an unusually broad registered trial programme for a compound at this stage, spanning rare mitochondrial-disease populations, ophthalmic endpoints, and cardiac-function measures. The entries below are described strictly by design and endpoint name; no result, effect size, or outcome is asserted for any of them, and each disease-relevant endpoint is stated purely as a study design feature.
MMPOWER-3 (Karaa et al., Neurology 2023; NCT03323749) was a Phase 3 randomised, double-blind, placebo-controlled, parallel-group trial in adults from a genetically confirmed primary mitochondrial-disorder population, with 1:1 randomisation over 24 weeks. Its co-primary endpoints are named only: change from baseline to week 24 in a walk-distance functional measure and in a symptom-assessment fatigue score. MMPOWER-2 (Karaa et al., 2020) was a randomised, double-blind, placebo-controlled crossover trial (N=30) in the same registered mitochondrial-disorder population, with a single named primary endpoint: a walk-distance functional measure. The earlier NCT02367014 was a completed Phase 1/2 randomised, placebo-controlled, double-blind trial (then coded MTP-131) in that population, with the named primary endpoint being change in a walk-distance functional measure from baseline to Day 5. TAZPOWER (NCT03098797) was a completed Phase 2/3 randomised, double-blind, placebo-controlled crossover trial in a genetically confirmed rare-disease population, followed by open-label treatment; its Part 1 primary endpoints are named only as a walk-distance functional measure and a symptom-assessment fatigue score.
The ReCLAIM cohorts (Mettu et al. and Allingham et al., 2021; PMID 36246181 and 36246187) were companion Phase 1 single-centre open-label 24-week trials in adults aged 55 and over within an ophthalmic research population, with the named primary endpoint being safety and tolerability alongside prespecified exploratory imaging and functional endpoints (named only). Preclinical work includes an in-vitro INS1 beta-cell study (Petcherski et al., 2018, PMID 30389435) with endpoints named only - mitochondrial morphology, mitophagosome formation and engulfment of mitochondria into autophagosomes - and an aged-mouse cardiac study (Whitson et al., 2021, PMID 34480713) profiling the S-glutathionylation and phosphorylation proteomes. Further registered trials exist (for example NCT02914665 and the ReNEW study NCT06373731) and are referenced by NCT only. Throughout this section the studies are listed by design and endpoint name; no result or effect is asserted.
The following are generic benchtop conventions for handling lyophilised research peptide, drawn from research-supply guidance rather than primary literature. They are quality-control and stability parameters for laboratory material, not directions for any use in humans or animals. Exact figures vary by supplier and lot, so always defer to the batch-specific certificate of analysis and supplier datasheet.
For storage, the unreconstituted lyophilised powder is commonly held frozen (typically around -20 C), protected from light and moisture. A reconstituted solution is generally kept refrigerated at 2-8 C. As a bench procedure, the lyophilised powder is dissolved in an appropriate aqueous laboratory solvent - for example deionised water or a suitable buffer - and allowed to dissolve without vigorous shaking. Final working concentration depends on solvent volume relative to peptide mass; this is a laboratory-solubilisation step, not a preparation method for any use in humans or animals. The reconstitution calculator helps researchers work out in-vitro stock concentrations for benchtop preparation.
Research-grade material is typically specified at greater than or equal to 98% purity by reversed-phase HPLC, with identity confirmed by mass spectrometry and, where stated, endotoxin screening. Purity and identity should be verifiable from documentation rather than assumed. A batch-specific certificate of analysis documenting HPLC purity, identity, and lot number is the standard quality-assurance record for reproducible in-vitro work.
Tier one, the firm ground: the chemistry is settled. The free-base identity (PubChem CID 11764719, CAS 736992-21-5, C32H49N9O5, 639.8 g/mol) resolves through four independent PubChem routes, the acetate salt is kept on its own CAS, and the four-residue tetrapeptide sequence is consistent across the primary literature. Tier two, the plausible middle: the cardiolipin-association mechanism rests on in-vitro biophysics, NMR and molecular-dynamics modelling, and cross-linking proteomics in model and isolated mitochondrial membranes - coherent, but a cell in a dish is not a person. Tier three, the thin part: the registered human programme is described here only by design and named endpoint, with no result or effect size reported on this page. It is not a licensed medicine, and it has not been shown to produce defined outcomes in humans. Curiosity is warranted; certainty is not.
SS-31 (elamipretide) supplied by Kovalabs is a laboratory research chemical intended for in-vitro and laboratory research use by qualified researchers only. It is not a medicine, food, cosmetic, or supplement, and is not for human or veterinary use, administration, or consumption. The molecular identity, mechanism summaries, study designs, and handling notes on this page are provided as scientific reference for research planning. They do not constitute medical, clinical, or dosing advice, and no therapeutic or clinical benefit is claimed or implied. Please read our full research disclaimer before purchase.
SS-31 (elamipretide) is a synthetic mitochondria-targeted tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH2. It is classified here by its molecular pharmacology, as a cationic, cardiolipin-associating inner-mitochondrial-membrane peptide, rather than by any indication. It is a research chemical for research use only, not for human or veterinary use.
Yes. PubChem CID 11764719, CAS 736992-21-5, molecular formula C32H49N9O5 and molecular weight 639.8 g/mol were cross-checked against four independent PubChem routes and all resolve to the same free-base molecule. The acetate salt carries a different CAS (1334953-95-5) and is kept separate from the free-base listing.
Yes. Elamipretide is the recommended INN; SS-31 and MTP-131 are research and development-code synonyms that map to the same record, PubChem CID 11764719 and CAS 736992-21-5. Branded trade names of separate investigational or licensed medicinal products are not applicable to this research-grade material.
In-vitro, biophysical and computational studies describe SS-31 as localising to the inner mitochondrial membrane and binding cardiolipin, partitioning into the membrane interfacial region and modulating membrane surface electrostatics, with cross-linking mass spectrometry mapping its mitochondrial protein interactors. These are mechanism and study-design descriptions only; no clinical effect or benefit is asserted.
As a general bench convention, the lyophilised powder is stored frozen (typically around -20 C) and protected from light and moisture, while a reconstituted solution is kept at 2-8 C. Reconstitution involves dissolving the powder in an appropriate aqueous laboratory solvent such as deionised water or a suitable buffer. These are laboratory-handling parameters only; always follow the batch-specific certificate of analysis. See the reconstitution guide for stock-concentration working notes.
No. SS-31 supplied by Kovalabs is for in-vitro laboratory research use only. It is not a medicine or supplement and is not for human or veterinary use, administration, or consumption. See our research disclaimer for full terms.