Comparison
FOXO4-DRI 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.
2074706-72-8
597562-32-8
Molecular weight
3735 g/mol
4493.33 g/mol
Half-life
0.5 h
no data
Sequence
D-Retro-Inverso-Variante eines FOXO4-Peptid-Fragments (LTLRKEPASEIAQSILEAYSQNGWANRRSGGKR — D-Aminosäuren in umgekehrter Sequenz)LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTESMechanism of action
FOXO4-DRI
FOXO4-DRI is the D-retro-inverso variant of a peptide fragment of the FOXO4 transcription factor. In senescent cells, FOXO4 is bound to p53, which suppresses p53-mediated apoptosis — the cells survive in a secreting 'zombie-like' state (senescence-associated secretory phenotype, SASP). The DRI peptide disrupts this FOXO4-p53 binding, freeing p53, and the senescent cell initiates apoptosis. Healthy cells are largely unaffected because p53 is not held back by FOXO4 in them. This selectivity was the central finding of the original 2017 publication.
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
Animal model
Human trial
Studies
3
4
of which in humans
0
1
Effects recorded
3
4
Open conflicts
1
1
Documented adverse events
1
0
Legal status
Full entries
Frequently asked questions
- What is the difference between FOXO4-DRI and LL-37?
- FOXO4-DRI is classified as "Research other", while LL-37 is classified as "Research other". FOXO4-DRI: Synthetic peptide with D-Retro-Inverso structure (all amino acids as D-form, sequence reversed), developed in 2017 as an experimental senolytic candidate. Goal: selective apoptosis of senescent cells via disruption of the FOXO4-p53 interaction. So far evaluated exclusively preclinically. 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, FOXO4-DRI or LL-37?
- The highest available evidence level is "Animal model" for FOXO4-DRI 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 FOXO4-DRI and LL-37 in Germany and the United States?
- Germany: FOXO4-DRI — Research only, LL-37 — Research only. United States: FOXO4-DRI — Research only, LL-37 — Research only. These are factual summaries with source and review date on the individual pages.