Comparison
Afamelanotide vs. LL-37
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
597562-32-8
Molecular weight
1646.87 g/mol
4493.33 g/mol
Half-life
12 h
no data
Sequence
Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTESMechanism 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.
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.
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
0
Legal status
Full entries
Frequently asked questions
- What is the difference between Afamelanotide and LL-37?
- Afamelanotide is classified as "Research other", while LL-37 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. 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. This page contrasts both neutrally and source-based — with no usage or dosing recommendation.
- Which peptide is better supported by science, Afamelanotide or LL-37?
- The highest available evidence level is "Human RCT" for Afamelanotide and "Human trial" for LL-37. 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 LL-37 in Germany and the United States?
- Germany: Afamelanotide — Prescription, LL-37 — Research only. United States: Afamelanotide — Prescription, LL-37 — Research only. These are factual summaries with source and review date on the individual pages.