LL-37
Medium EvidenceA human antimicrobial peptide studied for innate immunity, wound healing, and biofilm disruption.
What It Is
LL-37 is a 37-amino-acid peptide and the only cathelicidin-derived antimicrobial peptide found in humans. It is produced by neutrophils, macrophages, epithelial cells, and other immune tissues as part of the innate immune response. LL-37 demonstrates broad-spectrum antimicrobial activity against over 38 bacterial species, 16 fungi, and 16 viruses through mechanisms including membrane disruption, intracellular targeting, and biofilm suppression. Beyond its antimicrobial role, LL-37 modulates immune cell recruitment, promotes wound healing, and influences inflammatory signaling. A completed Phase 1 clinical trial of intra-tumoral LL-37 injections in melanoma patients with cutaneous metastases demonstrated significant anti-tumor potency, marking the first human clinical validation of LL-37's cancer applications. A key 2026 advancement is the development of LL-37 derivatives that overcome native limitations: the synthetic peptide CD4-PP, created through dimerization and backbone cyclization of LL-37, shows activity against common uropathogens, prevents new biofilm formation, and dissolves mature biofilm — addressing a critical unmet need in urinary tract infection treatment. A 2025 study published in ACS Biomaterials Science & Engineering reviewed systematic modification strategies for LL-37 derivatives with improved stability, reduced hemolytic activity, and enhanced efficacy under physiological salt concentrations. Current development in 2026 focuses on immobilization techniques, nanocarrier delivery systems, LL-37 derivative optimization, and synergistic combinations with existing antibiotics to combat multidrug-resistant infections. A comprehensive 2024 review in PubMed described LL-37 as 'the master antimicrobial peptide,' highlighting its multifaceted role from combating infections to cancer immunity. As of April 2026, the FDA removed LL-37 from the Category 2 bulk substances list, and it will be reviewed by the Pharmacy Compounding Advisory Committee (PCAC) at the July 2026 meeting.
Regulatory Status
Removed from Category 2 in the FDA's April 2026 reclassification. LL-37 is in the second PCAC session group (alongside Dihexa, GHK-Cu injectable, PEG-MGF, and Melanotan II) scheduled before February 2027 — not the July 23–24, 2026 session. Public comment docket open.
Effective: April 2026
View FDA SourceWhy Researchers Study It
LL-37 is the only human cathelicidin and represents a key component of innate immunity. Its broad-spectrum antimicrobial activity, combined with immunomodulatory and wound-healing properties, makes it a leading candidate for next-generation anti-infective therapies, particularly against multidrug-resistant biofilm-forming bacteria.
Proposed Mechanisms
- Disrupts bacterial membranes via electrostatic interaction with negatively charged lipid bilayers
- Forms oligomeric channels in membrane mimics, enabling membrane permeabilization
- Suppresses biofilm formation and disrupts established biofilms
- Recruits immune cells (neutrophils, monocytes) to infection sites via chemotactic signaling
- Modulates TLR signaling and NF-κB pathways to influence inflammatory responses
- Promotes angiogenesis and keratinocyte migration in wound healing contexts
Evidence Snapshot
| Study Type | Model | Outcome | Link |
|---|---|---|---|
| In vitro | Broad-spectrum antimicrobial panel | Effective against 38+ bacteria, 16 fungi, and 16 viruses; mechanisms include membrane rupture and biofilm suppression | Source |
| In vitro (2024) | Non-growing E. coli (stationary phase) | LL-37 retains potency against non-growing bacteria resistant to conventional antibiotics; slower killing kinetics than against log-phase cells | Source |
| Review (2025) | LL-37 derivative modifications — structure-activity relationships | Systematic modifications improve stability, reduce hemolytic activity, and enhance efficacy at physiological salt concentrations | Source |
| Human (Phase 1) | Intra-tumoral LL-37 in melanoma with cutaneous metastases | Significant anti-tumor potency demonstrated; first human clinical validation of LL-37 cancer applications | Source |
| In vitro (2026) | CD4-PP (cyclized LL-37 derivative) against uropathogens | Active against common uropathogens; prevents new biofilm formation and dissolves mature biofilm | Source |
Commonly Discussed Benefits
Researching LL-37? Track it, set reminders, and keep notes in the free app.
Safety & Cautions
- Native LL-37 has reduced efficacy under physiological salt concentrations
- Susceptible to proteolytic degradation in vivo
- Significant cytotoxicity to human cells at therapeutic concentrations — narrow therapeutic window
- Overexpression linked to inflammatory conditions such as rosacea and psoriasis
- Removed from FDA Category 2 in April 2026; PCAC review scheduled before February 2027 (second session, alongside Dihexa, GHK-Cu injectable, PEG-MGF, and Melanotan II)
- Not FDA-approved as a standalone antimicrobial therapy
Comparisons
See how LL-37 compares to related peptides:
Calculator Tools
Use our research tools to explore dosing and reconstitution data:
Citations
- [1] Vandamme D. et al. — A comprehensive summary of LL-37, the factotum human cathelicidin peptide. Cell Immunol. 2012 PubMed
- [2] Ridyard KE. & Bhatt A. — The potential of human peptide LL-37 as an antimicrobial and anti-biofilm agent. PMC. 2021 PubMed
- [3] Barman S. et al. — Exploring the antimicrobial potential of LL-37 derivatives. ACS Biomater Sci Eng. 2025 PubMed
- [4] Sánchez-Romero S. et al. — LL-37 is potent against non-growing E. coli. mSphere. 2024 PubMed
- [5] LL-37, the master antimicrobial peptide: multifaceted role from infections to cancer immunity — PubMed 2024 PubMed
- [6] A stable cyclized antimicrobial peptide derived from LL-37 with immunomodulatory effects — PMC 2022 PubMed
Keep researching in the app
- Log LL-37 to your private tracker
- Set a dosing reminder
- Compare it side-by-side with your stack
Related Peptides
BPC-157
Medium EvidenceA pentadecapeptide derived from human gastric juice, studied for tissue repair and gut-protective properties.
Thymosin Alpha-1
High EvidenceA thymic peptide approved in some countries for immune modulation, studied for viral infections and cancer adjunct therapy.
KPV
Medium EvidenceA tripeptide derived from alpha-MSH, studied for anti-inflammatory and gut-protective properties.
Zosurabalpin
Medium EvidenceA first-in-class tethered macrocyclic peptide antibiotic that kills carbapenem-resistant Acinetobacter baumannii (CRAB) by blocking the bacterium's lipopolysaccharide (LPS) transporter, now advancing into a global Phase 3 trial.
Difelikefalin
High EvidenceDifelikefalin (Korsuva in the U.S., Kapruvia in Europe) is a synthetic tetrapeptide built entirely from D-amino acids - D-Phe-D-Phe-D-Leu-D-Lys capped with a 4-aminopiperidine-4-carboxylic acid - that acts as a selective agonist at the kappa opioid receptor. Its defining property is what it cannot do: the molecule is hydrophilic and bulky enough that it does not meaningfully cross the blood-brain barrier, so it reaches kappa receptors on peripheral sensory nerve endings, keratinocytes and immune cells while leaving the central kappa receptors that produce dysphoria and hallucinations largely untouched. It has no activity at the mu opioid receptor, so it carries neither euphoria nor respiratory depression. In the Phase 3 KALM-1 and KALM-2 trials in hemodialysis patients with moderate-to-severe chronic-kidney-disease-associated pruritus, roughly 40-51% of difelikefalin-treated patients achieved a clinically meaningful (>=3-point) reduction on the 10-point Worst Itching Intensity NRS at 12 weeks versus roughly 20-28% on placebo. The FDA approved intravenous difelikefalin in August 2021; the EU approved it as Kapruvia in April 2022.