Side-by-side · Research reference
LL-37vsTesofensine
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AHuman-MechanisticHUMAN-REVIEWED15/35 cited
BPhase 3AUTO-DRAFTED10/40 cited
LL-37
Cathelicidin · Human AMP
Broad-spectrumAntimicrobial activity
Endogenous · Secreted at inflammation sites
Tesofensine
SNDRI · Phase 3 obesity candidate
Oral · Once daily morning
01Mechanism of Action
Parameter
LL-37
Tesofensine
Primary target
Serotonin / norepinephrine / dopamine transporters (SERT / NET / DAT)Astrup 2008
Pathway
hCAP-18 precursor → Proteinase-3 cleavage → LL-37 release → Membrane insertion/disruption
Triple monoamine reuptake inhibition → ↑synaptic 5-HT, NE, DA → appetite suppression + thermogenesisAstrup 2008
Downstream effect
Membrane permeabilization, cytokine induction, autophagy, phagosome-lysosome fusion, chemotaxisAhmad 2026Zhang 2026
Strong appetite suppression, mild thermogenic effect, weight lossAstrup 2008
Feedback intact?
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Origin
Endogenous human cathelicidin (37-AA fragment, residues 134–170 of hCAP-18)
Small molecule developed by NeuroSearch (Denmark) for CNS indications, repurposed for obesityAstrup 2008
Antibody development
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02Dosage Protocols
Parameter
LL-37
Tesofensine
Endogenous expression
Constitutive in neutrophils, epithelial tissues
Upregulated during infection and inflammation.Pinheiro 2026
—
Exogenous (experimental)
Dose varies by study; antimalarial ~10–50 μM in vitro
No FDA-approved exogenous formulation.
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Plasma levels (malaria)
Elevated in infected patients and miceHe 2026
Exogenous administration reduced parasitemia in murine models.He 2026
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Frequency
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Once daily, morning
Lower / starter dose
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0.125 mg / day
Duration
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24 weeks per studied cycle
Form
—
Oral capsule
Timing
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Morning to avoid sleep disruption
Half-life
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~9 days (very long)
04Side Effects & Safety
Parameter
LL-37
Tesofensine
Cytotoxicity (high dose)
Membrane disruption in host cells at supraphysiological concentrations
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Pro-inflammatory signaling
Can exacerbate inflammation in certain contexts (context-dependent)Pinheiro 2026
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Theoretical cancer risk
Immunomodulatory roles in tumor microenvironment under investigation
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Insomnia
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Dose-related; mitigate with morning timing
Dry mouth
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Common
Nausea
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Common
Mood changes
—
Anxiety / agitation possible
Cardiovascular events
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Phase 3 trial monitoring; not yet FDA-cleared
Pregnancy / OB
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Contraindicated
Absolute Contraindications
LL-37
—Tesofensine
- ·Pregnancy / breastfeeding
- ·Severe cardiovascular disease
- ·Concurrent MAOI use
Relative Contraindications
LL-37
- ·Active autoimmune disease (theoretical immune dysregulation)
Tesofensine
- ·Hypertension
- ·Anxiety disorder
- ·Insomnia
05Administration Protocol
Parameter
LL-37
Tesofensine
1. Natural secretion
LL-37 is constitutively expressed in neutrophils and epithelial cells, cleaved from hCAP-18 by proteinase-3 at sites of infection or inflammation.
Oral capsule (investigational; not commercial).
2. Experimental formulations
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.
Swallow whole with water, morning only.
3. Stability considerations
LL-37 is resistant to pepsin degradation at gastric pH. Synthetic short peptides designed to retain this stability while reducing toxicity.Lu 2026
Morning to mitigate insomnia. Do not dose evening.
4. Storage
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Room temp ≤25 °C, dry place.
5. Caveat
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Monitor BP + HR + mood. Avoid stimulants + MAOIs.