Comparison
Afamelanotide vs. MOTS-c
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
1627580-64-6
Molecular weight
1646.87 g/mol
2174.61 g/mol
Half-life
12 h
no data
Sequence
Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-ArgMechanism 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.
MOTS-c
MOTS-c arises from a short open reading frame located in the 12S rRNA region of the mitochondrial genome — unlike most peptides it is therefore not encoded by nuclear DNA. Mechanistically, preclinical work describes MOTS-c as modulating the folate cycle and the de novo purine biosynthesis tethered to it, thereby affecting the AMP/ATP ratio and, downstream, AMP-activated protein kinase (AMPK). Under metabolic stress, an AMPK-dependent translocation of the peptide into the cell nucleus and involvement in the regulation of stress-responsive genes (including via antioxidant-response-element-regulated transcription factors) have also been reported. These models derive predominantly from cell culture and rodents; the extent to which they reflect human physiology after administration of exogenous synthetic MOTS-c is not established by human studies.
Evidence base
Highest evidence
Human RCT
Human trial
Studies
4
4
of which in humans
4
1
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 MOTS-c?
- Afamelanotide is classified as "Research other", while MOTS-c 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. MOTS-c: MOTS-c is a 16-amino-acid mitochondrial-encoded peptide (mitochondrial-derived peptide, MDP) whose open reading frame lies within the 12S rRNA region of mitochondrial DNA. In basic research (including the laboratories of Changhan Lee and Pinchas Cohen) it is described as a regulator of metabolic homeostasis and an activator of the AMPK pathway, and is sometimes discussed as an 'exercise mimetic'. The evidence comes almost entirely from cell and animal models; controlled human trials of MOTS-c as a therapeutic are lacking. It is not approved as a medicine anywhere and is traded on the grey market as a research chemical. This page contrasts both neutrally and source-based — with no usage or dosing recommendation.
- Which peptide is better supported by science, Afamelanotide or MOTS-c?
- The highest available evidence level is "Human RCT" for Afamelanotide and "Human trial" for MOTS-c. 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 MOTS-c in Germany and the United States?
- Germany: Afamelanotide — Prescription, MOTS-c — Unapproved. United States: Afamelanotide — Prescription, MOTS-c — Unapproved. These are factual summaries with source and review date on the individual pages.