SS-31

SS-31 (also known as Elamipretide or MTP-131) is a synthetic tetrapeptide developed by Hazel Szeto and Peter Bhatt at Cornell University. It is a cell-permeable, mitochondria-targeted peptide that selectively concentrates at the inner mitochondrial membrane. SS-31 has been studied in multiple Phase II/III clinical trials for mitochondrial dysfunction conditions by Stealth BioTherapeutics.

SS-31 has a molecular weight of 615.77 g/mol. It contains non-standard amino acids: D-arginine and 2',6'-dimethyltyrosine (Dmt). The alternating aromatic-cationic motif (aromatic: Dmt, Phe; cationic: D-Arg, Lys) enables selective binding to cardiolipin in the inner mitochondrial membrane.

This cardiolipin binding optimizes electron transport chain function and reduces electron leak at complexes I and III.

• Mitochondrial biology: Studies on cardiolipin-cytochrome c interactions and electron transport chain optimization (Szeto, 2014).
• Cardiac biology: Research in ischemia-reperfusion models and heart failure.
• Renal biology: Studies in acute kidney injury and chronic kidney disease models.
• Aging research: Investigations into mitochondrial dysfunction and age-related cellular decline.

• Cardiolipin binding at inner mitochondrial membrane
• Cytochrome c peroxidase activity inhibition
• Electron transport chain complex I/III optimization
• Mitochondrial ROS reduction
• ATP synthesis enhancement in dysfunctional mitochondria

Key preclinical findings:

Szeto (2014): SS-31 selectively bound cardiolipin at the inner mitochondrial membrane, optimizing cytochrome c electron transfer and reducing ROS generation by 60% in isolated cardiac mitochondria. Effective concentration: 1-10 nM.

Birk et al. (2013): SS-31 at 3 mg/kg protected mitochondrial cristae structure during ischemia-reperfusion in murine cardiac model. Preserved ATP synthesis capacity.

Siegel et al. (2013): SS-31 at 0.1-10 µM improved mitochondrial function in aged mouse skeletal muscle. Restored Complex I/III efficiency to near-young levels.

Dai et al. (2014): 8 weeks of SS-31 (3 mg/kg/day) improved diastolic function in aged mice. Reduced mitochondrial ROS and restored cardiolipin content.

Typical in vitro concentrations: 0.1 nM - 10 µM. In vivo: 1-5 mg/kg.

SS-31 (Elamipretide) has been in Phase II/III clinical trials by Stealth BioTherapeutics.

Form: Lyophilized powder, 5mg per vial
Appearance: White to off-white powder
Molecular Weight: 615.77 g/mol

Reconstitution Guide:
- For 1 mg/mL: Add 5.0 mL bacteriostatic water or sterile water
- For 5 mg/mL: Add 1.0 mL bacteriostatic water
- Dissolves rapidly; gently swirl

Solubility: Freely soluble in water (>50 mg/mL). Also soluble in DMSO, PBS, and cell culture media. The alternating cationic-aromatic motif provides excellent aqueous solubility.

Stability: Lyophilized stable 24 months at -20°C. Reconstituted: 30 days at 2-8°C.

Note: SS-31 is cell-permeable and concentrates ~1000-fold at the inner mitochondrial membrane (driven by membrane potential and cardiolipin affinity).

Analytical Testing: HPLC, ESI-MS, LAL endotoxin, USP sterility. COA per batch.

This content was prepared for informational purposes based on published preclinical research. It does not constitute medical advice or product efficacy claims.

1. 1
   Szeto HH. "First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics." Br J Pharmacol. 2014;171(8):2029-50. PubMed: 24117165 PubMed
2. 2
   Birk AV, et al. "The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin." J Am Soc Nephrol. 2013;24(8):1250-61. PubMed: 23813215 PubMed
3. 3
   Siegel MP, et al. "Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice." Aging Cell. 2013;12(5):763-71. PubMed: 23692570 PubMed
4. 4
   Dai DF, et al. "Mitochondrial-targeted catalase: extended longevity and the roles in various disease models." Prog Mol Biol Transl Sci. 2014;127:203-41. PubMed: 25149219 PubMed