SS31 50mg

▎SS-31 Structure

▎SS-31 Research

Molecular Background

Elamipretide (SS-31) is a synthetic tetrapeptide with the sequence D-Arg-2',6'-dimethylTyr-Lys-Phe-NH₂. PubChem lists elamipretide under CID 11764719, with the molecular formula C32H49N9O5 and a molecular weight of approximately 639.8 g/mol. Published research has examined its interaction with cardiolipin and other mitochondrial components under defined experimental conditions.[1,8]

Research Progress

Beatrice Vahle and colleagues used female Zucker fatty spontaneously hypertensive heart failure F1 hybrid lean rats (n = 10, control group) and obese rats (n = 24, HFpEF group). At 20 weeks of age, the HFpEF rats were randomized to receive either sodium chloride (n = 12) or elamipretide (n = 12) for 12 weeks. Skeletal muscle tissue was then evaluated using whole-muscle force testing, single-fiber mechanics, mitochondrial respiration, histology, and molecular analyses. The authors reported reduced cardiolipin levels and tafazzin expression in HFpEF rats, together with contractile dysfunction, titin hyperphosphorylation, fiber atrophy, and increased oxidative-stress markers. In the elamipretide group, the investigators reported differences in whole-muscle and single-fiber contractile measurements, titin phosphorylation, and fiber size. They proposed that cardiolipin-associated changes in oxidative phosphorylation may contribute to the mitochondrial and contractile findings observed in this rat model.[2]

Silvia Russo and colleagues studied SS-31 in a tafazzin-knockdown (TazKD) mouse model characterized by abnormal cardiolipin remodeling and mitochondrial alterations. Cardiac mitochondria were evaluated for membrane ultrastructure, mitochondrial dynamics, mitophagy-related proteins, respiratory activity, and respiratory-chain supercomplex organization. The authors reported changes in mitochondrial morphology, selected proteins involved in mitochondrial dynamics and autophagy, respiratory measurements, and supercomplex assembly in SS-31-treated TazKD mice compared with untreated TazKD animals.[3]

Gavin Pharaoh and colleagues treated aged male mice with elamipretide (ELAM) by osmotic minipump for approximately 8 weeks and compared mitochondrial and physiological measurements with those from untreated aged and young mice. The investigators assessed muscle strength, cardiac function, mitochondrial responses to ADP, and proteins involved in ADP/ATP transport and synthesis. They reported increased ADP sensitivity in aged muscle mitochondria after ELAM exposure, together with changes in muscle force and cardiac systolic function. Protein abundance in the ADP/ATP transport pathway was not substantially changed, while reduced S-glutathionylation of several proteins, including adenine nucleotide translocase (ANT), was reported. The authors also examined direct interactions of ELAM with ANT and ATP synthase as part of the proposed mechanistic framework.[4]

Fig1. ADP-stimulated respiration and membrane-potential measurements in isolated muscle mitochondria in the cited study.[4]

The source figure illustrates the ADP/ATP transport pathway and the experimental hexokinase-clamp and cytochrome-c conditions used to measure oxygen-consumption and membrane-potential responses in isolated muscle mitochondria. ANT, VDAC, ATP synthase, and related pathway components are shown as presented by the study authors. Group sizes, concentrations, statistical methods, and complete procedures are provided in the original publication.[4]

Yue-Ming Zhang and colleagues subjected adult C57BL/6J mice to 21 days of chronic sleep deprivation using a rotating-wheel protocol while administering SS-31 or saline under the study design. Hippocampus-dependent behavior was evaluated using novel-object-recognition and Morris water-maze testing, and molecular analyses included mitochondrial, inflammatory, and synaptic markers. The authors reported differences in behavioral measurements and in SIRT1, PGC-1α, NF-κB, inflammatory cytokines, brain-derived neurotrophic factor, postsynaptic density protein-95, and synaptophysin in the SS-31 study group compared with sleep-deprived controls. These findings were obtained in a mouse model of chronic sleep deprivation.[5]

Fig2. Morris water-maze measurements reported after SS-31 exposure in the chronic sleep-deprivation mouse model.[5]

The source figure compares learning-phase escape latency, swimming velocity, platform crossings, and time- and distance-based measurements during the memory phase among the experimental groups. Statistical comparisons and complete study conditions are reported in the original publication.[5]

Mengying Suo and colleagues established a pressure-overload model in mice using transverse aortic constriction (TAC) and evaluated SS31 in wild-type and Sirt3-knockout animals and fibroblasts. The authors reported differences in cardiac-function and myocardial-fibrosis measurements in wild-type mice exposed to SS31, together with changes in optic atrophy protein 1 (OPA1) and other proteins involved in mitochondrial dynamics. In Sirt3-knockout mice and fibroblasts, several SS31-associated responses observed in the wild-type model were not reproduced. The study therefore linked the reported experimental findings to Sirt3-associated mitochondrial fusion under the conditions tested.[7]

Fig3. Myocardial-fibrosis measurements reported in wild-type and Sirt3-knockout mice in the SS31 pressure-overload study.[7]

Masson staining images of each group; (B) Masson staining statistical analysis of the degree of fibrosis between tissues; (C) Masson staining statistical analysis of the degree of perivascular fibrosis (n = 5, *p < 0.05, WT + TAC vs. WT + sham; #p < 0.05, WT + TAC + SS31 vs. WT + TAC; &p < 0.05, Sirt3KO + TAC vs. Sirt3KO + sham); (D) Immunohistochemical staining images of collagen I, collagen III, TGF-β and α-SMA in each group (bar = 20 μm); (E–H) collagen I and collagen III immunohistochemical staining statistical analysis. (The results are expressed as the means ± SEM, n = 5. The one-way ANOVA test was used, and n represents the number of independent experiments. *p < 0.05 vs. WT + sham group; #p < 0.05 vs. WT + TAC group; &p < 0.05 vs. Sirt3KO + sham group).

Research Limitations

The studies summarized above use different preclinical systems, including HFpEF rats, tafazzin-deficient mice, aged mice, chronic sleep-deprivation mice, and pressure-overload cardiac models. Results from these models are not directly interchangeable, and differences in species, disease model, exposure schedule, formulation, tissue context, and measured endpoints can influence the observations reported. A 2026 study examining PEG-modified SS31 described rapid renal elimination and limited pharmacokinetic exposure of unmodified SS31 as formulation challenges, illustrating that distribution and exposure can also affect interpretation of preclinical results.[6]

Elamipretide is also the active ingredient in the FDA-approved prescription drug Forzinity, which received accelerated approval in 2025 for a specific Barth syndrome indication and drug product. That approval applies to the approved Forzinity formulation and labeled use and does not establish equivalence, safety, efficacy, or approved status for independently supplied SS-31 research materials.[1,9]

COCER Peptides presents SS-31 solely for laboratory research and analytical use. It is not intended for human or veterinary use. The research described above summarizes findings reported in third-party publications and does not represent a claim regarding the clinical performance, safety, efficacy, diagnosis, treatment, or approved use of any COCER Peptides material.

▎Relevant Citations

References

[1] Shirley M. Elamipretide: First Approval[J]. Drugs, 2026,86(3):377-383.

DOI:10.1007/s40265-025-02269-8.

[2] Vahle B, Weidner S, Tomalka A, et al. Targeting Mitochondrial Dysfunction With Elamipretide (SS-31) Improves Skeletal Muscle Performance in a HFpEF Rat Model[J]. Circulation: Heart Failure, 2026,19(8):e014397.

DOI:10.1161/circheartfailure.126.014397.

[3] Russo S, De Rasmo D, Rossi R, et al. SS-31 treatment ameliorates cardiac mitochondrial morphology and defective mitophagy in a murine model of Barth syndrome[J]. Scientific Reports, 2024,14:13655.

DOI:10.1038/s41598-024-64368-y.

[4] Pharaoh G, Kamat V, Kannan S, et al. The mitochondrially targeted peptide elamipretide (SS-31) improves ADP sensitivity in aged mitochondria by increasing uptake through the adenine nucleotide translocator (ANT)[J]. GeroScience, 2023,45(6):3529-3548.

DOI:10.1007/s11357-023-00861-y.

[5] Zhang Y M, Wang Y T, Wei R M, et al. Mitochondrial antioxidant elamipretide improves learning and memory impairment induced by chronic sleep deprivation in mice[J]. Brain and Behavior, 2024,14(5):e3508.

DOI:10.1002/brb3.3508.

[6] Wen Y, Zhao Z, Zheng X, et al. Topology-Controlled PEGylation Enhances Renal Accumulation of Therapeutic Peptide for Treating Ischemia–Reperfusion Injury[J]. Nano Letters, 2026,26(26):8566-8573.

DOI:10.1021/acs.nanolett.6c01908.

[7] Suo M, Qi Y, Liu L, et al. SS31 Alleviates Pressure Overload-Induced Heart Failure Caused by Sirt3-Mediated Mitochondrial Fusion[J]. Frontiers in Cardiovascular Medicine, 2022,9.

DOI:10.3389/fcvm.2022.858594.

[8] NCBI PubChem. Elamipretide. PubChem CID 11764719.

[9] U.S. Food and Drug Administration. FDA Grants Accelerated Approval to First Treatment for Barth Syndrome. September 19, 2025.

ALL PRODUCTS, ARTICLES, TECHNICAL MATERIALS, PRODUCT DESCRIPTIONS, AND OTHER INFORMATION PROVIDED ON THIS WEBSITE ARE INTENDED SOLELY FOR LEGITIMATE LABORATORY RESEARCH, INFORMATIONAL, AND EDUCATIONAL PURPOSES.

Products offered by Cocer Peptides are intended exclusively for in vitro and laboratory research and are NOT intended for human or veterinary use, human consumption, clinical use, diagnostic use, therapeutic use, compounding, self-administration, injection, or any other form of administration to humans or animals. These products are not intended to diagnose, treat, cure, mitigate, or prevent any disease or medical condition, nor are they intended to affect the structure or function of the human or animal body. Unless expressly stated otherwise, products offered on this website have not been evaluated or approved by the U.S. Food and Drug Administration (FDA) for human or veterinary use. Any references to published studies, biochemical pathways, molecular mechanisms, or experimental findings are provided solely for scientific discussion and research purposes and do not constitute medical advice, therapeutic claims, dosing guidance, or instructions for use. Purchasers are solely responsible for ensuring that all products are acquired, handled, stored, used, and disposed of in accordance with applicable laws, regulations, institutional requirements, and laboratory safety standards.