SS-31 Research

What SS-31 is

SS-31 is a synthetic tetrapeptide, and elamipretide, MTP-131 and Bendavia are three further names for the same molecule ^[21][25]. PubChem resolves each name, and the CAS number 736992-21-5, to the same record, CID 11764719 ^[21]. The sequence is D-Arg-Dmt-Lys-Phe-NH2, where Dmt is 2,6-dimethyltyrosine, and every residue is L except arginine, which is D ^[1][21].

The formula is C32H49N9O5 and the free base molecular weight is 639.8 ^[21]. The approved pharmaceutical product is a different form, the trihydrochloride salt, whose molecular weight is 749.2 ^[1][21]. Listings often print 749.2 as the peptide's own molecular weight, but that figure belongs to the salt.

Regulatory status, stated in full

The usual statement that a compound is not approved for human therapeutic use is not accurate for this molecule.

The molecule holds a United States approval granted on 19 September 2025, and that approval is accelerated rather than full ^[1][2][3]. It covers one rare inherited mitochondrial disorder, Barth syndrome, in patients weighing at least 30 kg ^[1]. It rests on an intermediate endpoint, knee extensor muscle strength, not on a demonstrated clinical outcome ^[1]. The label states that continued approval may be contingent on verification of clinical benefit in a confirmatory trial ^[1]. That confirmatory trial began recruiting in July 2026, with primary completion estimated for 2029 ^[22].

The approval attaches to a regulated prescription product and to that one disease. It does not extend to research-grade material, to any other condition, or to any other compound.

European status is a designation, not an approval. Elamipretide holds an EU orphan designation for Barth syndrome, EU/3/21/2430, designated on 20 May 2021 ^[26]. The register states that orphan designation does not mean a medicine is authorized for use ^[26].

The pivotal evidence is very small

(human) The approval rests on TAZPOWER, a randomized, double-blind, placebo-controlled crossover trial in 12 patients ^[4]. The authors state that in part 1 neither primary endpoint was met, and improvements on both measures appeared only in part 2, the uncontrolled open-label extension ^[4]. The label records that the drug was not superior to placebo on those primary endpoints ^[1].

(human) A 168-week open-label extension reported a cumulative 96.1 m gain on the six-minute walk test against extension baseline ^[5]. There was no placebo group, and 8 of 10 entrants reached that timepoint ^[5]. (human) A retrospective study compared 8 treated patients with 19 untreated historical controls ^[6]. It reported a 79.7 m walk difference and a 40.8 N strength difference by handheld dynamometry at week 64 ^[6]. Propensity matching cannot correct for unmeasured confounding.

The largest trial failed

(human) MMPOWER-3 was a phase 3 randomized, double-blind, placebo-controlled trial in 218 adults with primary mitochondrial myopathy ^[7]. It missed both co-primary endpoints at 24 weeks, and the six-minute walk difference of -3.2 m (95% CI -18.7 to 12.3; p=0.69) numerically favored placebo ^[7]. The fatigue score difference was -0.07 (95% CI -0.10 to 0.26; p=0.37) ^[7]. The authors report Class I evidence that elamipretide does not improve those endpoints ^[7]. The registry lists the trial as terminated, with the sponsor citing the missed primary endpoints ^[7]. The open-label extension of MMPOWER-2 was terminated for the same stated reason ^[7].

(human) The two earlier steps also missed: MMPOWER, in 36 adults, returned p=0.053 on its unadjusted primary comparison ^[10]. (human) MMPOWER-2, in 30 patients, returned a 19.8 m difference (95% CI -2.8 to 42.5; p=0.0833) ^[9]. (human) A post hoc genotype subgroup of the failed phase 3 reported a trend in one nuclear-DNA group ^[8]. Post hoc subgroups of null trials are hypothesis-generating only, as that paper states ^[8]. (human) NuPOWER, the 102-patient trial built to test that hypothesis, completed in December 2024 ^[23]. No results were posted and no publication was located as of 28 August 2026, which is an absence of evidence, not a reported failure ^[23].

Every other indication tested has also missed

(human) PROGRESS-HF, in 71 patients with reduced ejection fraction, found no effect on left ventricular end-systolic volume (p=0.90 and p=0.28) ^[11]. (human) An earlier phase 1 single-infusion study in 36 patients reported volume reductions in the highest-exposure cohort only, which the adequately powered trial then failed to confirm ^[11][12]. (human) EMBRACE STEMI was negative on its primary endpoint and on every prespecified secondary ^[13]. (human) ReCLAIM-2, in 176 patients with dry age-related macular degeneration, missed both primary endpoints ^[14].

The approval is for a single-gene cardiolipin remodeling defect, and it is not evidence that acting on mitochondria produces clinical benefit. This molecule failed in every other mitochondrial indication tested ^{[7][9][10][11][13][14]}.

Mechanism is well characterized, and mechanism is not outcome

(in vitro, animal) SS-31 binds cardiolipin at the inner mitochondrial membrane and inhibits the cytochrome c peroxidase reaction that drives cardiolipin peroxidation ^[16]. In rats it protected cristae during renal ischemia and accelerated ATP recovery on reperfusion ^[16]. (in vitro) Biophysical work shows it partitions into the membrane interfacial region and modulates surface electrostatics, so it is not a conventional free-radical scavenger ^[17]. (in vitro, animal) A genome-scale CRISPR screen identified PLSCR3 as essential for its protective effect, and knockout abrogated that effect in mice ^[18]. The molecular target is still being revised.

(animal) In 14 dogs with induced heart failure, elamipretide improved ejection fraction and mitochondrial respiration measures ^[19]. That result did not transfer to people, and PROGRESS-HF was null ^[11][19]. The mechanistic review cited here was written by the peptide's inventor, who founded the developing company ^[20].

Human pharmacology, safety and conflicts

(human) Label pharmacokinetics describe roughly 92% absolute subcutaneous bioavailability and low plasma protein binding ^[1]. Metabolism proceeds by sequential C-terminal degradation to inactive fragments, and urinary recovery is essentially complete within 48 hours in patients with normal renal function ^[1]. Elimination is renal, and exposure rises substantially in renal impairment ^[1]. The label states no terminal half-life, so none should be quoted.

(human) A randomized trial found that a single infusion marginally raised skeletal muscle ATPmax immediately afterward, an effect of borderline significance (p=0.055 and p=0.045 on the two tests) ^[15]. There was no difference by day 7 and no change in fatigue resistance ^[15].

(human) In the controlled crossover, local administration reactions occurred in all 12 patients on drug and in 8 of 12 on placebo ^[1]. The label carries hypersensitivity warnings and a benzyl alcohol contraindication in neonates ^[1]. Near-universal injection-site reactions also make genuine blinding doubtful in small crossover trials ^[1]. Stealth BioTherapeutics sponsored essentially the entire clinical program described here ^[1][4][5][7].

Aging, athletic performance and general mitochondrial support in healthy people have not been tested in controlled trials. A 2026 sports medicine review covering SS-31 and similar grey-market peptides concludes that rigorous human safety data are scarce, and there is potential for serious harm to patients ^[24]. Research-grade material is not a medicine and is not for human consumption.

Frequently Asked Questions

Is SS-31 the same molecule as elamipretide? Yes. SS-31, elamipretide, MTP-131 and Bendavia are four names for one molecule ^[21][25]. PubChem resolves each of those names to the same record, CID 11764719 ^[21].

SS-31 is described as FDA approved. What does that approval actually cover? It is an accelerated United States approval granted on 19 September 2025 ^[1][2][3]. It covers Barth syndrome only, in patients weighing at least 30 kg ^[1]. It was granted on an intermediate endpoint, knee extensor muscle strength, and continued approval may be contingent on a confirmatory trial that is not expected to complete before 2029 ^[1][22]. The pivotal program comprised 12 patients, and the randomized part of that trial met neither primary endpoint ^[1][4].

What did the largest human trial of SS-31 find? MMPOWER-3 randomized 218 adults with primary mitochondrial myopathy and missed both co-primary endpoints at 24 weeks ^[7]. The six-minute walk difference was -3.2 m (p=0.69) and the fatigue difference was -0.07 (p=0.37) ^[7]. The authors report Class I evidence that elamipretide does not improve those endpoints, and the trial was terminated for that reason ^[7].

Which molecular weight is correct for SS-31? The free base molecular weight is 639.8, for the formula C32H49N9O5 ^[21]. The figure 749.2 is the molecular weight of the trihydrochloride salt used in the approved pharmaceutical product, so it should not be printed as the peptide's own weight ^[1][21].

References

1. 1

   US Food and Drug Administration. Approved prescribing information, elamipretide injection. NDA 215244, approval date 20250919, label effective 20251210. Retrieved via field-qualified openFDA queries.
2. 2

   Zhao C. Drug Discoveries & Therapeutics, 2026. PMID 41260682.; DOI: 10.5582/ddt.2025.01111 (Letter).
3. 3

   Shirley M. Drugs, 2026. PMID 41335372.; DOI: 10.1007/s40265-025-02269-8.
4. 4

   Reid Thompson W. Genetics in Medicine, 2021. PMID 33077895.; DOI: 10.1038/s41436-020-01006-8.
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   Thompson WR. Genetics in Medicine, 2024. PMID 38602181.; DOI: 10.1016/j.gim.2024.101138.
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   Hornby B. Orphanet Journal of Rare Diseases, 2022. PMID 36056411.; DOI: 10.1186/s13023-022-02469-5.
7. 7

   Karaa A. Neurology, 2023. PMID 37268435.; DOI: 10.1212/WNL.0000000000207402. Registry records NCT03323749 (MMPOWER-3) and NCT02976038 (SPIMM-203, the MMPOWER-2 open-label extension), both retrieved 28 August 2026.
8. 8

   Karaa A. Orphanet Journal of Rare Diseases, 2024. PMID 39574155.; DOI: 10.1186/s13023-024-03421-5.
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   Karaa A. Journal of Cachexia, Sarcopenia and Muscle, 2020. PMID 32096613.; DOI: 10.1002/jcsm.12559.
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    Karaa A. Neurology, 2018. PMID 29500292.; DOI: 10.1212/WNL.0000000000005255.
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    Butler J. Journal of Cardiac Failure, 2020. PMID 32068002.; DOI: 10.1016/j.cardfail.2020.02.001.
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    Daubert MA. Circulation: Heart Failure, 2017. PMID 29217757.; DOI: 10.1161/CIRCHEARTFAILURE.117.004389.
13. 13

    Gibson CM. European Heart Journal, 2016. PMID 26586786.; DOI: 10.1093/eurheartj/ehv597.
14. 14

    Ehlers JP. Ophthalmology Science, 2025. PMID 39605874.; DOI: 10.1016/j.xops.2024.100628.
15. 15

    Roshanravan B. PLoS One, 2021. PMID 34264994.; DOI: 10.1371/journal.pone.0253849.
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    Birk AV. Journal of the American Society of Nephrology, 2013. PMID 23813215.; DOI: 10.1681/ASN.2012121216.
17. 17

    Mitchell W. Journal of Biological Chemistry, 2020. PMID 32273339.; DOI: 10.1074/jbc.RA119.012094.
18. 18

    Silvaroli JA. Journal of the American Society of Nephrology, 2024. PMID 38530359.; DOI: 10.1681/ASN.0000000000000338. Published correction PMID 38990651.; DOI: 10.1681/ASN.0000000000000454.
19. 19

    Sabbah HN. Circulation: Heart Failure, 2016. PMID 26839394.; DOI: 10.1161/CIRCHEARTFAILURE.115.002206.
20. 20

    Szeto HH. British Journal of Pharmacology, 2014. PMID 24117165.; DOI: 10.1111/bph.12461.
21. 21

    NCBI PubChem. CID 11764719 (free base) and CID 137528200 (trihydrochloride); CAS 736992-21-5; UNII 87GWG91S09. Retrieved 28 August 2026.
22. 22

    ClinicalTrials.gov registry record, NCT07531251. Status verified July 2026.
23. 23

    ClinicalTrials.gov registry record, NCT05162768. Record retrieved 28 August 2026.
24. 24

    Mendias CL. Sports Medicine, 2026. PMID 41966639.; DOI: 10.1007/s40279-026-02437-0.
25. 25

    Tung C. International Journal of Molecular Sciences, 2025. PMID 39940712.; DOI: 10.3390/ijms26030944.
26. 26

    European Medicines Agency. Orphan designation EU/3/21/2430, elamipretide, treatment of Barth syndrome; designated 20 May 2021, status positive. Public register entry retrieved 28 August 2026.