SS-31
Metabolic
ABOUT
Elamipretide (SS-31) is a mitochondria-targeting tetrapeptide. Early randomised clinical studies have examined short-term physiological and clinical measures in selected populations.
EVIDENCE OVERVIEW
Early human findings, not yet confirmed
WHAT THIS MEANS
Potential. Review the research and limitations before relying on this record.
IDENTITY
HALF-LIFE
HOW IT IS THOUGHT TO WORK
Elamipretide (SS-31, MTP-131) is a tetrapeptide that concentrates in the inner mitochondrial membrane by binding cardiolipin. Binding prevents cardiolipin from converting cytochrome c into a peroxidase while preserving its electron-carrying function, which is proposed to restore efficiency of the electron transport chain and ATP production.
PHARMACOKINETICS
Phase 3 used 40 mg once daily subcutaneously over 24 weeks. Discrete half-life and clearance values are not curated here; a post-hoc analysis found only a weak positive correlation between plasma elamipretide concentration and six-minute-walk improvement, which itself argues against a simple exposure-response relationship.
REVIEW
PUBLISHED PAIR RECORDS
with MOTS-c
Converging on mitochondrial functionMOTS-c and Elamipretide (SS-31) both act on mitochondrial biology, so their proposed effects converge rather than complement. Elamipretide is the only one of this group tested in a large controlled human trial, and MMPOWER-3 did not meet either primary endpoint; the mitochondrial-derived peptide in this pair has no interventional human data at all. Their mechanisms differ within the same organelle - cardiolipin binding on the inner membrane versus retrograde signalling to the nucleus - so overlap is at the level of target tissue rather than target molecule. No study has characterised this combination. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 21 Aug 2026with Humanin
Converging on mitochondrial functionHumanin and Elamipretide (SS-31) both act on mitochondrial biology, so their proposed effects converge rather than complement. Elamipretide is the only one of this group tested in a large controlled human trial, and MMPOWER-3 did not meet either primary endpoint; the mitochondrial-derived peptide in this pair has no interventional human data at all. Their mechanisms differ within the same organelle - cardiolipin binding on the inner membrane versus retrograde signalling to the nucleus - so overlap is at the level of target tissue rather than target molecule. No study has characterised this combination. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 21 Aug 2026HUMAN EVIDENCE
This compound has been properly tested and the pivotal trial failed. MMPOWER-3, a phase 3 randomised double-blind placebo-controlled trial in 218 patients with primary mitochondrial myopathy, did not meet either primary endpoint: the six-minute-walk difference was -3.2 metres (p=0.69) and the fatigue-score difference -0.07 (p=0.37). A post-hoc genotype analysis found a six-minute-walk benefit in the chronic progressive external ophthalmoplegia subgroup (37.3 versus -8.0 metres, p=0.0024), which is hypothesis-generating rather than confirmatory. Smaller randomised studies have reported physiological effects - improved in-vivo mitochondrial ATP production in older adults after a single dose, and short-term cardiac measures in heart failure - without a demonstrated clinical outcome.
REPORTED EFFECTS
Treatment was well tolerated in MMPOWER-3, with most adverse events mild to moderate. Injection-site reactions are the characteristic finding for subcutaneous dosing. This is one of the few compounds in this catalogue with adverse-event data from a large controlled trial.
RESEARCH LIMITATIONS
Early or small trials do not establish broad clinical benefit or long-term safety. Findings are indication- and formulation-specific, and do not support off-label dosing guidance.
CURATED SOURCES · 5