SS-31 (Elamipretide)

1 Identity

Synthetic aromatic-cationic tetrapeptide amide containing one D-residue and one non-proteinogenic residue. Position 1 is D-arginine; position 2 is 2',6'-dimethyl-L-tyrosine (Dmt); positions 3 and 4 are L-lysine and L-phenylalanine; the C-terminus is a primary carboxamide, not a free acid. Three basic centers (alpha-amino, guanidino, lysine epsilon-amino), so the article is always a salt and counterion stoichiometry is measured rather than assumed. No cysteine, no disulfide. As of September 2025 the molecule is the active moiety of an FDA-approved drug product. Part of the Szeto-Schiller (SS) aromatic-cationic tetrapeptide series.

Sequence

H-D-Arg-Dmt-Lys-Phe-NH2. Four residues, N to C: position 1 D-arginine, the D-enantiomer and not L; position 2 2',6'-dimethyl-L-tyrosine, a non-proteinogenic residue carrying two aryl methyl groups on the tyrosine ring; position 3 L-lysine; position 4 L-phenylalanine. Free alpha-amino N-terminus, no N-acetyl. C-terminus is a primary carboxamide. No one-letter string is adequate for this molecule and none should be accepted on a certificate: a written "RYKF" silently discards both the D-configuration at position 1 and the two aryl methyls at position 2, and those are the only two features that separate this article from cheaper isomers that share its mass exactly.

Molecular formula

C32H49N9O5 (free base). Research-channel material is normally the acetate or trifluoroacetate; the clinical substance is the hydrochloride.

Average mass

639.802 Da for the free base C32H49N9O5, on IUPAC 2021 abridged conventional atomic weights. Published figures for the same formula print 639.80, which is the same number to the precision stated.

Monoisotopic mass

639.38567 Da free base; [M+H]+ 640.39294; [M+2H]2+ 320.70011. A single-ion match at 640.4 is not identity on this molecule and must never be presented as such: at least three distinct chemical entities share 639.802 / 639.38567 exactly. Formula and both masses follow from residue-by-residue reconstruction of the stated structure, and that is the limit of what arithmetic reaches. The stereochemistry lies outside it: the D-configuration at position 1 and the two aryl methyls at position 2 cannot be established by any mass or formula, so a certificate that reports only formula and mass has not established the identity of this article.

Salt / variant note

Salt forms are the commercially distinct articles and they do not share a mass. Free base C32H49N9O5 639.802 / 639.38567. Mono-hydrochloride C32H50ClN9O5 676.26 / 675.3624; di-hydrochloride C32H51Cl2N9O5 712.72 / 711.3390; tri-hydrochloride C32H52Cl3N9O5 749.18 / 747.3157 — three basic centers, so stoichiometry is measured, never assumed. Mono-acetate C34H53N9O7 699.854 / 699.40680; di-acetate C36H57N9O9 759.91 / 759.4279. Mono-TFA C34H50F3N9O7 753.83 / 753.3785; di-TFA C36H51F6N9O9 867.848 / 867.37139; tri-TFA C38H52F9N9O11 981.87 / 981.3643. At tri-TFA the free base is only 65.2 percent of the powder. Then the isobars, which are the real hazard. SS-02, also written [Dmt1]DALDA, is Dmt-D-Arg-Phe-Lys-NH2: the same four residues in a different order, identical formula C32H49N9O5, identical 639.802 / 639.38567, a constitutional isomer that no mass measurement at any resolving power distinguishes and only MS/MS fragment ordering or co-injection against an authentic standard separates. The all-L analog with L-Arg at position 1 is likewise C32H49N9O5, identical mass, and co-elutes on achiral RP-HPLC. Mass-resolvable relatives: SS-01 (DALDA, Tyr-D-Arg-Phe-Lys-NH2) and des-dimethyl SS-31, plain tyrosine in place of Dmt, are both C30H45N9O5 at 611.748 / 611.35437, 28.05 Da light — Dmt is the costly building block and 611.7 on a certificate means tyrosine was used. The mono-methyl intermediate C31H47N9O5 is 625.78 / 625.3700. The des-amido free acid C32H48N8O6 is 640.786 / 640.36968, 0.98 Da heavy and invisible to any instrument reporting "640". Dmt phenol oxidation products carry the ordinary +15.999 increment.

2 Class & testing panel

Form

Single article

Testing panel

P3 — panel definition

3 Primary sources & evidence

The index reports the design and provenance of the literature, not a conclusion about effect.

The literature is unusually well developed for a molecule sold in this market, and it points in more than one direction. In vitro: cardiolipin binding on the inner mitochondrial membrane (Birk et al., J Am Soc Nephrol 2013, PMID 23813215), membrane surface electrostatics (Mitchell et al., J Biol Chem 2020, PMID 32273339), and a mechanistic review (Szeto, Br J Pharmacol 2014, PMID 24117165). Regulatory: accelerated approval September 2025 as FORZINITY for Barth syndrome in patients weighing 30 kg or more, reviewed at Shirley, Drugs 2026, PMID 41335372; the human efficacy base for that approval is TAZPOWER, NCT03098797, Phase 2/3, n=12, completed — a very small trial appropriate to an ultra-rare disease. The most important item is A negative one and the citation index leads with it: the Phase 3 in primary mitochondrial myopathy, NCT03323749, n=218, is TERMINATED, and its open-label extension NCT02976038, n=28, likewise, the registry recording "The registration trial did not meet primary endpoints." Any marketing that cites that program without also carrying its outcome is a red flag. Other completed programs: HFrEF NCT02788747 (n=71); STEMI/reperfusion as Bendavia NCT01572909 (n=300); dry AMD ReCLAIM-2 NCT03891875 (n=176); skeletal muscle function in the elderly NCT02245620 (n=41); Friedreich ataxia NCT05168774 (n=20); Leber hereditary optic neuropathy NCT02693119 (n=12); Fuchs' corneal endothelial dystrophy NCT02653391 (n=22). Recruiting: NCT07275424 (Phase 2, n=30) and 4TAZPower NCT07531251 (Phase 4, n=48). Twenty-one registered studies in total. Preclinical senescence work is in vitro only (PMIDs 42456009, 42450582). Absences stated as absences: no independent non-sponsor randomized human trial was identified, and no human trial at all in the uses that drive research-market interest.

4 Storage & specification

Storage

Lyophilized salt at -20 degrees C plus or minus 5 degrees C, desiccated, in amber glass under an inert headspace. The 2',6'-dimethyltyrosine phenol is the oxidation-sensitive point of the molecule and light protection is not optional; the label states that reason rather than leaving it to habit. Reconstituted solutions are treated as single-use.

Shelf life

Provisional 24-month retest interval at -20 degrees C plus or minus 5 degrees C in the sealed original container. It is provisional pending this company's own stability data, and total oxidized species is trended by name as the governing attribute, because the failure route on this sequence is phenol oxidation rather than hydrolysis.