Side-by-side · Research reference
DihexavsLL-37
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AAnimal-StrongHUMAN-REVIEWED7/28 cited
BHuman-MechanisticHUMAN-REVIEWED15/35 cited
Dihexa
Angiotensin IV Analogue · Pre-Clinical
Not established — animal studies only
LL-37
Cathelicidin · Human AMP
Broad-spectrumAntimicrobial activity
Endogenous · Secreted at inflammation sites
01Mechanism of Action
Parameter
Dihexa
LL-37
Primary target
c-Met receptor (HGF receptor tyrosine kinase)
Pathway
HGF/c-Met receptor activation → downstream signaling cascade → synaptogenesis and dendritic arborization
hCAP-18 precursor → Proteinase-3 cleavage → LL-37 release → Membrane insertion/disruption
Downstream effect
Induction of dendritic arborization, synapse formation, neurogenesis, and neuroprotection in rodent models
Membrane permeabilization, cytokine induction, autophagy, phagosome-lysosome fusion, chemotaxisAhmad 2026Zhang 2026
Feedback intact?
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Origin
Small-molecule angiotensin IV analogue designed to activate HGF/c-Met systemWright 2015
Endogenous human cathelicidin (37-AA fragment, residues 134–170 of hCAP-18)
Antibody development
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02Dosage Protocols
Parameter
Dihexa
LL-37
Human dosing
Not established — no human trials
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Animal studies
Mouse/rat models only — dosing not translatable to humans
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Evidence basis
Pre-clinical / Rodent models
In vitro, animal models, human observational
Clinical status
No Phase 1, 2, or 3 trials published
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Endogenous expression
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Constitutive in neutrophils, epithelial tissues
Upregulated during infection and inflammation.Pinheiro 2026
Exogenous (experimental)
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Dose varies by study; antimalarial ~10–50 μM in vitro
No FDA-approved exogenous formulation.
04Side Effects & Safety
Parameter
Dihexa
LL-37
Human safety data
None available — no human clinical trials
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Theoretical c-Met risks
c-Met receptor activation has been implicated in tumorigenesis; unknown cancer risk profile
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Pre-clinical tolerability
Not systematically reported in available studies
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Cytotoxicity (high dose)
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Membrane disruption in host cells at supraphysiological concentrations
Pro-inflammatory signaling
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Can exacerbate inflammation in certain contexts (context-dependent)Pinheiro 2026
Theoretical cancer risk
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Immunomodulatory roles in tumor microenvironment under investigation
Absolute Contraindications
Dihexa
- ·Not approved for human use — research compound only
LL-37
—Relative Contraindications
Dihexa
- ·Theoretical contraindication: active or history of malignancy (c-Met pathway involvement in cancer)
LL-37
- ·Active autoimmune disease (theoretical immune dysregulation)
05Administration Protocol
Parameter
Dihexa
LL-37
1. Human administration
No established protocol. Dihexa has not been tested in human subjects. Animal studies used various routes (typically subcutaneous or intraperitoneal in rodents) not translatable to clinical use.
LL-37 is constitutively expressed in neutrophils and epithelial cells, cleaved from hCAP-18 by proteinase-3 at sites of infection or inflammation.
2. Legal status
Pre-clinical research compound. Not approved by FDA or any regulatory authority for human use.
Synthetic LL-37 and derivatives (e.g., SAMP-12aa) tested in vitro and animal models. Administered via topical, intraperitoneal, or intravenous routes in research settings.
3. Stability considerations
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LL-37 is resistant to pepsin degradation at gastric pH. Synthetic short peptides designed to retain this stability while reducing toxicity.Lu 2026