Comparison
LL-37 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.
597562-32-8
1627580-64-6
Molecular weight
4493.33 g/mol
2174.61 g/mol
Half-life
no data
no data
Sequence
LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTESMet-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-ArgMechanism of action
LL-37
LL-37 is a cationic, amphipathic helical peptide and the only member of the cathelicidin family in humans. It is generated by proteolytic cleavage from the C-terminal portion of the precursor protein hCAP18 (CAP-18). Mechanistically it associates with and can permeabilize microbial membranes; in addition it modulates immune cells, influences cytokine release, exerts chemotactic activity, and can bind extracellular self-DNA. Preclinical models have described both anti-inflammatory and pro-inflammatory effects, depending on concentration and tissue context.
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
4
4
of which in humans
1
1
Effects recorded
4
4
Open conflicts
1
1
Documented adverse events
0
1
Legal status
Full entries
Frequently asked questions
- What is the difference between LL-37 and MOTS-c?
- LL-37 is classified as "Research other", while MOTS-c is classified as "Research other". LL-37: LL-37 is the only known human cathelicidin, a 37-amino-acid antimicrobial peptide generated by cleavage of the precursor protein hCAP18. In research it plays a central role in innate immune defence and wound healing, yet acts in a context-dependent manner as both anti- and pro-inflammatory and has been linked to autoimmune processes. LL-37 is not an approved drug; the evidence base is predominantly basic and preclinical. 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, LL-37 or MOTS-c?
- The highest available evidence level is "Human trial" for LL-37 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 LL-37 and MOTS-c in Germany and the United States?
- Germany: LL-37 — Research only, MOTS-c — Unapproved. United States: LL-37 — Research only, MOTS-c — Unapproved. These are factual summaries with source and review date on the individual pages.