# Elamipretide (SS-31) vs MOTS-c - Canonical: https://residue.info/vs/elamipretide-vs-mots-c/ - Compounds: Elamipretide (https://residue.info/c/elamipretide/), MOTS-c (https://residue.info/c/mots-c/) - Updated: 2026-10-19 · Reviewed by: Residue Editorial Team Both are linked to mitochondria but are otherwise unalike. Elamipretide (SS-31) is a synthetic cardiolipin-binding tetrapeptide with FDA accelerated approval as Forzinity for Barth syndrome [1]. MOTS-c is a 16-residue peptide encoded in mitochondrial DNA; given to mice, it prevented diet-induced obesity and insulin resistance [2], but no human treatment results are published and it is not FDA-approved [3]. ## Side by side | | Elamipretide | MOTS-c | |---|---|---| | Origin | Synthetic tetrapeptide [4] | Encoded in the mitochondrial 12S rRNA gene [2] | | Mechanism | Mitochondrial cardiolipin binder [1] | Folate-cycle inhibition → AMPK activation [2] | | Human trials | TAZPOWER, MMPOWER-3, heart failure [5][6][7] | Phase 2 in prediabetes recruiting [8] | | Key result | 6MWT +95.9 m in Barth open-label phase [5] | Better physical capacity in old mice [9] | | Negative result | MMPOWER-3 missed endpoints [6] | — | | FDA | Accelerated approval: Forzinity [10] | Withdrawn nomination; no human exposure data [3] | | Evidence grade | A | D | ## How are the two molecules different? Elamipretide is a synthetic four-residue peptide containing a modified tyrosine [4], described in its label as a mitochondrial cardiolipin binder [1]. MOTS-c is encoded by a short open reading frame in the mitochondrial 12S rRNA gene; in muscle cells it inhibits the folate cycle and activates AMPK [2]. ## What have elamipretide trials shown? In Barth syndrome, TAZPOWER's randomized crossover part missed both primary endpoints, but at 36 weeks of open-label treatment the 6-minute walk improved by 95.9 m [5], sustained at 96.1 m over 168 weeks in 8 patients [11]. FDA's accelerated approval rests on knee-extensor strength [1]. In primary mitochondrial myopathy, MMPOWER-3 (218 adults) found no benefit over placebo [6]. A single infusion in heart failure was well tolerated and reduced left-ventricular volumes at the highest dose [7]. ## What is the evidence for MOTS-c? MOTS-c treatment prevented age- and diet-related insulin resistance and diet-induced obesity in mice [2] and improved physical performance in young, middle-aged and old mice [9]. In humans, exercise raised endogenous MOTS-c [9], and plasma levels were similar in lean and obese adults [12]. No human treatment results are published; a phase 2 trial in prediabetes is recruiting [8]. ## Are they FDA-approved? Forzinity (elamipretide) received FDA accelerated approval in September 2025 [10][13]. FDA lists MOTs-C among withdrawn compounding nominations and has identified no human exposure data [3]. ## Frequently asked questions **Is SS-31 the same as MOTS-c?** No. SS-31 (elamipretide) is a synthetic tetrapeptide that binds cardiolipin [1]; MOTS-c is a naturally encoded 16-amino-acid mitochondrial peptide [2]. **Which has human evidence?** Elamipretide, from randomized trials in Barth syndrome, primary mitochondrial myopathy and heart failure [5][6][7]. MOTS-c human studies measure natural levels [12]; a treatment trial is recruiting [8]. **Is elamipretide approved for anti-aging or energy?** No. Its only approved indication is to improve muscle strength in Barth syndrome patients weighing at least 30 kg, under accelerated approval [1]. **Can you take elamipretide and MOTS-c together?** No published trial among the sources we cite tested them together. Elamipretide (Forzinity) is labeled only for Barth syndrome under accelerated approval [1]; MOTS-c has no approved indication [3]. ## Sources [1] FORZINITY prescribing information: Indications and Usage. FDA-approved labeling via openFDA/DailyMed, version effective 2025-12-10. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=146bf34c-76f2-48db-ac07-fb29cce2cd75 [2] The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Lee C et al. Cell Metab. 2015. https://pubmed.ncbi.nlm.nih.gov/25738459/ [3] Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026. https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks [4] PubChem compound record: Elamipretide. C32H49N9O5 · MW 639.8 g/mol. https://pubchem.ncbi.nlm.nih.gov/compound/11764719 [5] A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism. Reid Thompson W et al. Genet Med. 2021. https://pubmed.ncbi.nlm.nih.gov/33077895/ [6] Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. Karaa A et al. Neurology. 2023. https://pubmed.ncbi.nlm.nih.gov/37268435/ [7] Novel Mitochondria-Targeting Peptide in Heart Failure Treatment: A Randomized, Placebo-Controlled Trial of Elamipretide. Daubert MA et al. Circ Heart Fail. 2017. https://pubmed.ncbi.nlm.nih.gov/29217757/ [8] MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity. Hudson Biotech · PHASE2 · recruiting. https://clinicaltrials.gov/study/NCT07505745 [9] MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Reynolds JC et al. Nat Commun. 2021. https://pubmed.ncbi.nlm.nih.gov/33473109/ [10] Drugs@FDA: FORZINITY (NDA215244). STEALTH BIOTHERAPS; original approval 2025-09-19; Prescription. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=215244 [11] Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER. Thompson WR et al. Genet Med. 2024. https://pubmed.ncbi.nlm.nih.gov/38602181/ [12] Plasma MOTS-c levels are associated with insulin sensitivity in lean but not in obese individuals. Cataldo LR et al. J Investig Med. 2018. https://pubmed.ncbi.nlm.nih.gov/29593067/ [13] Elamipretide: First Approval. Shirley M Drugs. 2026. https://pubmed.ncbi.nlm.nih.gov/41335372/ --- From Residue. Research and education only; not medical advice. Quote with attribution and a link to the canonical page.