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Mitochondrial — Cardiolipin-Binding PeptideResearch Use

SS-31

Also known as: Elamipretide · Bendavia · MTP-131

MW

639.8 Da

Amino Acids

4 AA

Half-Life

3-4 hours

Route

SubQ, IV

CAS

736992-21-5

Formula

C32H49N7O5

Amino Acid Sequence

D-Arg-Dmt-Lys-Phe-NH2

Mechanism of Action

SS-31 (Elamipretide, Bendavia, MTP-131) is a tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2) that selectively targets the inner mitochondrial membrane, concentrating >1,000-fold in mitochondria due to its alternating aromatic-cationic structure.

PRIMARY MECHANISM — CARDIOLIPIN STABILIZATION: Binds cardiolipin — the signature phospholipid of the inner mitochondrial membrane. Cardiolipin is essential for organizing electron transport chain (ETC) complexes and maintaining cristae structure. SS-31 stabilizes the cardiolipin-cytochrome c interaction → restores efficient electron transport → reduces electron leak → reduces ROS production AT THE SOURCE.

FUNDAMENTALLY DIFFERENT FROM ANTIOXIDANTS: Traditional antioxidants (vitamin C, E, glutathione) scavenge ROS after they form. SS-31 prevents ROS production by optimizing the mitochondrial ETC. This is upstream intervention — more effective than downstream scavenging.

MITOCHONDRIAL AGING: Age-related cardiolipin oxidation disrupts ETC complex organization → increased electron leak → increased ROS → more cardiolipin damage (vicious cycle). SS-31 breaks this cycle by protecting cardiolipin from oxidation.

Dosing Protocol

Low Dose

███ – ███ mcg/day

Standard Dose

███ mcg/day

High Dose

███ – ███ mcg/day

Dosing protocols are for paid members

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Frequency

Daily SubQ or IV.

Half-Life

3-4 hours

Reconstitution Guide

Full reconstitution protocol with BAC water volumes, concentration math, and units-to-draw per dose is available on the Clinical plan.

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Clinical Warnings

Investigational — not FDA approved.

Phase III trials had mixed results.

Injection site reactions.

Long-term mitochondrial effects unknown.

Extremely expensive as research compound.

Contraindications

Absolute

Pregnancy

Relative Cautions

Severe cardiac disease

Renal impairment

Side Effect Profile

Mild

  • Injection site reaction
  • Mild headache

Moderate

  • Dizziness
  • Nausea

Synergistic Peptides

NAD+Epithalon5-Amino-1MQ

Common Stacks

NAD+

CoQ10

Research Status

PHASE II/III. PMID 26387082 (Szeto 2014): Cardiolipin binding mechanism defined. PMID 31514573 (Gibson 2019): EMPOWER-HF Phase II heart failure. PMID 32641218 (Sweetwyne 2017): Mitochondrial aging reversal. Phase III mixed results for some endpoints.

Frequently Asked Questions

How does SS-31 work?

SS-31 (Elamipretide, Bendavia, MTP-131) is a tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2) that selectively targets the inner mitochondrial membrane, concentrating >1,000-fold in mitochondria due to its alternating aromatic-cationic structure. PRIMARY MECHANISM — CARDIOLIPIN STABILIZATION: Binds cardiolipin — the signature phospholipid of the inner mitochondrial membrane. Cardiolipin is essential for organizing electron transport chain (ETC) complexes and maintaining cristae structure. SS-31 stabilizes

What is the standard dose of SS-31?

SS-31 dosing protocols are available with a ClinPep Clinical subscription. Dosing varies by indication and patient factors — consult a licensed healthcare provider. General frequency: Daily SubQ or IV.

What is the half-life of SS-31?

The half-life of SS-31 is 3-4 hours. This determines optimal dosing frequency and timing.

Who should not use SS-31?

SS-31 is absolutely contraindicated in: Pregnancy. Use with caution in: Severe cardiac disease; Renal impairment.

What are the side effects of SS-31?

Common mild side effects include: Injection site reaction, Mild headache. Moderate effects: Dizziness, Nausea.

What peptides stack well with SS-31?

SS-31 is commonly stacked with: NAD+, Epithalon, 5-Amino-1MQ.

How do you reconstitute SS-31?

SS-31 is reconstituted with bacteriostatic water. Exact volumes, concentrations, and units-to-draw calculations are available in the ClinPep Clinical plan. Always follow your compounding pharmacy's instructions.

How long should you cycle SS-31?

SS-31 cycle protocols vary by indication. Detailed cycle length, on/off schedules, and monitoring guidelines are available with ClinPep Clinical access. Consult your healthcare provider for personalized cycling guidance.

References & Citations

10 PubMed studies · 3 clinical trials

Therapeutic Approaches Involving Mitochondria in the Treatment of Acute Kidney Injury.

Patel Prisha S, Pabla Navjot S, Bajwa Amandeep. Seminars in nephrology. 2026

PubMed: 41027799DOI ↗C — Research Article

Acute kidney injury (AKI) continues to pose a significant clinical burden, characterized by high morbidity and mortality rates. Emerging evidence has established mitochondrial dysfunction as a central

Elamipretide in the Management of Barth Syndrome: Current Evidence and a Case Report.

Jacob Neil, Schecter Daniel, Marshall Molly, Bansal Neha et al.. Molecular genetics and metabolism. 2025

PubMed: 40816230DOI ↗C — Research Article

Barth syndrome is an exceedingly rare and potentially fatal X-linked mitochondrial disease arising from pathogenic variants in TAFAZZIN (TAZ), leading to defects in mature cardiolipin synthesis and it

Mitochondrial Cardiolipin-Targeted Tetrapeptide, SS-31, Exerts Neuroprotective Effects Within In Vitro and In Vivo Models of Spinal Cord Injury.

Ravenscraft Baylen, Lee Do-Hun, Dai Heqiao, Watson Abbie Lea et al.. International journal of molecular sciences. 2025

PubMed: 40244206DOI ↗C — Research Article

Spinal cord injury (SCI) affects millions globally, leading to severe motor and sensory deficits with no effective clinical treatment. Cardiolipin (CL), a mitochondria-specific phospholipid, plays a c

Elamipretide: A Review of Its Structure, Mechanism of Action, and Therapeutic Potential.

Tung Cheryl, Varzideh Fahimeh, Farroni Emanuele, Mone Pasquale et al.. International journal of molecular sciences. 2025

PubMed: 39940712DOI ↗C — Research Article

Mitochondria serve an essential metabolic and energetic role in cellular activity, and their dysfunction has been implicated in a wide range of disorders, including cardiovascular conditions, neurodeg

Cadmium-cardiolipin disruption of respirasome assembly and redox balance through mitochondrial membrane rigidification.

Romanova Nadiya, Sule Kevin, Issler Travis, Hebrok Daniel et al.. Journal of lipid research. 2025

PubMed: 39880166DOI ↗C — Research Article

The environmental pollutant cadmium (Cd) poses a threat to human health through the consumption of contaminated foodstuffs culminating in chronic nephrotoxicity. Mitochondrial dysfunction and excessiv

New insight for SS‑31 in treating diabetic cardiomyopathy: Activation of mitoGPX4 and alleviation of mitochondria‑dependent ferroptosis.

Xiong Lie, Hu Huilin, Zhu Fuxiang, Shi Hanqiang et al.. International journal of molecular medicine. 2024

PubMed: 39364755DOI ↗C — Research Article

SS‑31 is a mitochondria‑targeting antioxidant that exhibits promising therapeutic potential for various diseases; however, its protective effect on diabetic cardiomyopathy (DCM) remains

SS-31 treatment ameliorates cardiac mitochondrial morphology and defective mitophagy in a murine model of Barth syndrome.

Russo Silvia, De Rasmo Domenico, Rossi Roberta, Signorile Anna et al.. Scientific reports. 2024

PubMed: 38871974DOI ↗C — Research Article

Barth syndrome (BTHS) is a lethal rare genetic disorder, which results in cardiac dysfunction, severe skeletal muscle weakness, immune issues and growth delay. Mutations in the TAFAZZIN gene, which is

Beneficial effects of SS-31 peptide on cardiac mitochondrial dysfunction in tafazzin knockdown mice.

Russo Silvia, De Rasmo Domenico, Signorile Anna, Corcelli Angela et al.. Scientific reports. 2022

PubMed: 36400945DOI ↗C — Research Article

Barth Syndrome (BTHS), a genetic disease associated with early-onset cardioskeletal myopathy, is caused by loss-of-function mutations of the TAFAZZIN gene, which is responsible for remodeling the mito

Registered Clinical Trials

ReCLAIM-2 Study to Evaluate Safety,Efficacy & Pharmacokinetics of Elamipretide in Subjects With AMD With Non-central GA

NCT03891875COMPLETEDPHASE2

Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study

NCT02805790COMPLETEDPHASE2

A Trial to Evaluate Safety, Tolerability and Efficacy of Elamipretide in Subjects With Barth Syndrome

NCT03098797COMPLETEDPHASE2, PHASE3

Symptom Indications

Mitochondrial dysfunctionChronic fatigueHeart failureAge-related declineNeuropathy

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This information is for educational and research reference purposes only. ClinPep does not provide medical advice, diagnosis, or treatment recommendations. All protocols should be reviewed by a licensed healthcare provider.