Comparison
Afamelanotide vs. Elamipretide
Two peptides side-by-side — identity, evidence base, legal status and known adverse events.
Identity
Category
Research other
Research other
CAS no.
75921-69-6
736992-21-5
Molecular weight
1646.87 g/mol
639.8 g/mol
Half-life
12 h
no data
Sequence
Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2D-Arg-Dmt-Lys-Phe-NH2Mechanism of action
Afamelanotide
Afamelanotide is a synthetic analogue of α-melanocyte-stimulating hormone. It differs from native α-MSH by two substitutions — norleucine at position 4 and D-phenylalanine at position 7 — which make it metabolically more stable and more potent. As an agonist at the melanocortin-1 receptor (MC1R) on melanocytes, it activates adenylate cyclase, raises cAMP and increases tyrosinase activity via the transcription factor MITF. This shifts pigment synthesis toward eumelanin, which absorbs UV and visible light and has antioxidant properties — the presumed mechanism of photoprotection in EPP.
Elamipretide
Elamipretide is a cell-permeable tetrapeptide with alternating aromatic and basic residues that selectively concentrates on cardiolipin — a phospholipid found almost exclusively in the inner mitochondrial membrane that is important for cristae curvature and the organisation of the respiratory-chain complexes. By binding cardiolipin, elamipretide is proposed to stabilise cristae architecture, support electron transport and ATP production, and reduce the formation of reactive oxygen species. These mechanistic models derive largely from cell and animal models and biophysical work; the extent to which they explain clinical efficacy in humans is, given the mixed trial results, a matter of ongoing research.
Evidence base
Highest evidence
Human RCT
Human RCT
Studies
4
4
of which in humans
4
4
Effects recorded
4
4
Open conflicts
1
1
Documented adverse events
4
1
Legal status
Full entries
Frequently asked questions
- What is the difference between Afamelanotide and Elamipretide?
- Afamelanotide is classified as "Research other", while Elamipretide is classified as "Research other". Afamelanotide: Afamelanotide (brand name Scenesse) is a synthetic 13-amino-acid analogue of α-melanocyte-stimulating hormone (α-MSH) and a melanocortin-1 receptor agonist. Unlike most peptides covered here, it is a regularly approved medicine: EMA approval in 2014/2015, FDA approval in 2019, in each case as a subcutaneous implant for the prevention of phototoxicity in adults with erythropoietic protoporphyria (EPP). It promotes eumelanin formation in the skin. Elamipretide: Elamipretide (SS-31, MTP-131, formerly Bendavia) is a synthetic, mitochondria-targeting tetrapeptide (sequence D-Arg-Dmt-Lys-Phe-NH2) that binds cardiolipin on the inner mitochondrial membrane and is proposed to stabilise cristae structure and support mitochondrial bioenergetics. It was investigated clinically by Stealth BioTherapeutics across several indications, including primary mitochondrial myopathy, Barth syndrome, heart failure, and dry age-related macular degeneration (geographic atrophy). The trial record is mixed, with several pivotal studies missing their primary endpoints. In September 2025 elamipretide (brand name Forzinity) received accelerated FDA approval in the United States solely for the ultra-rare Barth syndrome; for all other investigated indications it remains investigational and it is not approved as a medicine outside the United States. This page contrasts both neutrally and source-based — with no usage or dosing recommendation.
- Which peptide is better supported by science, Afamelanotide or Elamipretide?
- The highest available evidence level is "Human RCT" for Afamelanotide and "Human RCT" for Elamipretide. A higher evidence level means more robust data, but says nothing about suitability for an individual. The full body of evidence is on each peptide's own page.
- What is the legal status of Afamelanotide and Elamipretide in Germany and the United States?
- Germany: Afamelanotide — Prescription, Elamipretide — Unapproved. United States: Afamelanotide — Prescription, Elamipretide — Prescription. These are factual summaries with source and review date on the individual pages.