Comparison
Melanotan II 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.
121062-08-6
1627580-64-6
Molecular weight
1024.18 g/mol
2174.61 g/mol
Half-life
1 h
no data
Sequence
Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-ArgMechanism of action
Melanotan II
Melanotan II binds non-selectively to all five melanocortin-receptor subtypes (MC1R-MC5R). Via MC1R in melanocytes, eumelanin synthesis is stimulated (pigmenting effect). Via MC4R and MC3R in the CNS, appetite, sexual function and blood pressure are modulated. The cyclic structure and D-amino acids increase stability compared to natural α-MSH.
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 trial
Human trial
Studies
9
4
of which in humans
5
1
Effects recorded
4
4
Open conflicts
1
1
Documented adverse events
6
1
Legal status
Full entries
Frequently asked questions
- What is the difference between Melanotan II and MOTS-c?
- Melanotan II is classified as "Research other", while MOTS-c is classified as "Research other". Melanotan II: Cyclic hepta-peptide and non-selective melanocortin-receptor agonist. Originally researched at the University of Arizona as a sun-protection concept — never approved as a medicine. Widespread on the black market; regulatory warnings for cardiovascular and oncological risks. 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, Melanotan II or MOTS-c?
- The highest available evidence level is "Human trial" for Melanotan II 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 Melanotan II and MOTS-c in Germany and the United States?
- Germany: Melanotan II — Unapproved, MOTS-c — Unapproved. United States: Melanotan II — Unapproved, MOTS-c — Unapproved. These are factual summaries with source and review date on the individual pages.