Data edition of
Residue An evidence-graded reference for peptide science

Monograph in Immune & host-defense peptides

LL-37

The only human cathelicidin, an antimicrobial peptide made by the body. As a drug it has been tested as a topical treatment for leg ulcers, with mixed results.

Also called Cathelicidin LL-37 · hCAP18 (precursor) · CAMP

B

Best evidence: Randomized human trials

Two randomized, placebo-controlled trials of topical LL-37 in venous leg ulcers: a 34-patient first-in-man trial was positive at lower doses; a 148-patient phase IIb trial missed its primary analysis.

Not FDA-approved · FDA compounding nomination withdrawn

Residue Editorial Team · updated

What is LL-37?

LL-37 is the human cathelicidin, an antimicrobial peptide with immunomodulatory and pro-angiogenic properties1PubMedLL-37 but Not 25-Hydroxy-Vitamin D Serum Level Correlates with Healing of Venous Leg Ulcers. Krejner A et al. Arch Immunol Ther Exp (Warsz). 2017.. Topical LL-37 improved healing of venous leg ulcers at lower doses in a 34-patient randomized trial2PubMedTreatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial. Grönberg A et al. Wound Repair Regen. 2014., but a 148-patient phase IIb trial found no overall benefit3PubMedEvaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial. Mahlapuu M et al. Wound Repair Regen. 2021.. It is not FDA-approved, and FDA records nonclinical safety concerns4FDACertain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026..

PubMed records
2,412247 reviews
Trial publications
5736 tagged RCT
Registered studies
202 active · 1 phase 3
Molecular weight
4,493g/mol · PubChem
Evidence grade
BRandomized human trials

Key findings

  1. First-in-man RCT (34 patients): healing-rate constants roughly six- and threefold higher than placebo at 0.5 and 1.6 mg/mL; 3.2 mg/mL did no better than placebo2.
  2. HEAL LL-37 phase IIb (148 patients): no significant improvement in healing in the full population; benefit appeared only in a post hoc subgroup with large wounds3.
  3. Both doses were well tolerated in both trials2,3.
  4. In 19 patients with leg ulcers, serum LL-37, but not vitamin D, correlated with healing rate1.
  5. FDA lists cathelicidin LL-37 among withdrawn compounding nominations, citing nonclinical findings of detrimental effects on male reproduction and possible protumorigenic effects in some tissues4.

Written by Residue Editorial Team

Reviewed by Residue Editorial Team · source-by-source check,

First published

Last updated

Registry data · How we grade · Markdown + sources

What is LL-37, chemically?

Identifiers retrieved from PubChem.
PubChem CID16198951 “LL-37”
FormulaC205H340N60O53
Molecular weight4,493 g/mol
CAS (as listed)154947-66-7
FDA UNII3DD771JO2H
InChIKeyPOIUWJQBRNEFGX-XAMSXPGMSA-N
Length37 residues
Route in trialsTopical solution to ulcers (trials)
MechanismAntimicrobial host-defense peptide with immunomodulatory and pro-angiogenic activity
  • Hydrophobic
  • Polar
  • Basic (+)
  • Acidic (−)
  • Gly / Pro / Cys
Figure 1. Residue sequence of LL-37 (37 positions) as recorded in PubChem CID 16198951 — H-Leu-Leu-Gly-Asp-Phe-Phe-Arg-Lys-Ser-Lys-Glu-Lys-Ile-Gly-Lys-Glu-Phe-Lys-Arg-Ile-Val-Gln-Arg-Ile-Lys-Asp-Phe-Leu-Arg-Asn-Leu-Val-Pro-Arg-Th….

What is LL-37?

LL-37 is the human cathelicidin, a small antimicrobial peptide that also has immunomodulatory and pro-angiogenic properties, so it may promote wound healing; its expression is controlled by factors including vitamin D1. PubChem lists the 37-residue sequence beginning LLGDFFRKSK, formula C205H340N60O535PubChemPubChem compound record: LL-37. C205H340N60O53 · MW 4493 g/mol.. It is strongly expressed at the edge of acute wounds but only weakly in chronic wounds6PubMedStability of the cathelicidin peptide LL-37 in a non-healing wound environment. Grönberg A et al. Acta Derm Venereol. 2011..

How is LL-37 thought to work?

As a host-defense peptide it is antimicrobial, and it also acts on inflammation and blood-vessel growth1. A concern for topical use was that enzymes in chronic wounds would destroy it. In the lab, trypsin degraded it completely but matrix metalloproteinase-9 did not, and it resisted breakdown in fluid from non-healing ulcers for up to 24 hours6.

What have studies found?

First-in-man trial. Thirty-four people with hard-to-heal venous leg ulcers had a 3-week placebo run-in, then 4 weeks of randomized, double-blind treatment twice weekly. Healing rates were about six times placebo at 0.5 mg/mL and three times at 1.6 mg/mL, with mean ulcer area falling 68% and 50%; 3.2 mg/mL was no better than placebo2.

Phase IIb. HEAL LL-37 randomized 148 patients (mean age 67.6, median ulcer duration 20.3 months) to 0.5 or 1.6 mg/mL or placebo with compression. It found no significant improvement in healing overall. A post hoc analysis suggested benefit in wounds of at least 10 cm², which would need a new, adequately powered trial3.

Registered trials. Many ClinicalTrials.gov records measure natural LL-37 levels rather than give the peptide7TrialClinicalTrials.gov registry search: LL-37. 20 registered studies at fetch..

Is LL-37 FDA-approved?

Table 1. Regulatory status of LL-37 in the United States — from Drugs@FDA (openFDA) and FDA’s bulk-substance compounding categories, as fetched.
RecordStatusSource
FDA approval No approved application Drugs@FDA returned no application for “LL-37”. openFDA
Compounding: nominated, then withdrawn
Cathelicidin LL-37		 Withdrawn nomination FDA still lists its safety concerns:
“Compounded drugs containing cathelicidin LL-37 may pose risk for immunogenicity for certain routes of administration and may have complexities with regard to peptide-related impurities and API characterization. FDA lacks sufficient safety-related information regarding cathelicidin LL-37 to know whether the drug would cause harm when administered to humans. Nonclinical research findings suggest detrimental effects on…”		 4

FDA lists "Cathelicidin LL-37" among substances whose compounding nominations were withdrawn. It notes immunogenicity risk, impurity and characterization complexities, a lack of safety information in humans, and nonclinical findings suggesting detrimental effects on male reproduction and that it can be protumorigenic in some tissues4. Drugs@FDA returned no application.

What is still unknown?

  • Whether it helps large ulcers, the subgroup flagged post hoc3.
  • Any injected use. The trials we found were topical2,3.

What effects has LL-37 shown, by body system?

Each row is graded separately using the Residue evidence scale: a compound can carry an A for one use and a D for another.

Table 2. Research-observed effects of LL-37 by body system, with the strongest evidence available for each.
SystemWhat was observedGrade
Venous leg ulcers (topical)Positive dose-response in a 34-patient RCT2; no overall benefit in a 148-patient phase IIb RCT3. B
Stability in woundsFairly resistant to breakdown in chronic-wound fluid ex vivo6. D
Natural levelsSerum level correlated with ulcer healing in 19 patients (observational)1. D

How much research is there on LL-37?

083166 1996: 1 records 1996 1997: 2 records 1998: 6 records 1999: 5 records 2000: 9 records 2000 2001: 11 records 2002: 20 records 2003: 25 records 2004: 32 records 2005: 53 records 2005 2006: 64 records 2007: 52 records 2008: 73 records 2009: 92 records 2010: 90 records 2010 2011: 122 records 2012: 116 records 2013: 113 records 2014: 133 records 2015: 140 records 2015 2016: 130 records 2017: 142 records 2018: 142 records 2019: 144 records 2020: 166 records 2020 2021: 155 records 2022: 148 records 2023: 116 records 2024: 126 records 2025: 148 records 2025 2026: 151 records (year to date) 2026
Figure 2. PubMed records per publication year matching ("LL-37"[tiab] AND (peptide OR cathelicidin)) — 2,412 in total; peak 166 in 2020. The 2026 bar is year-to-date (hatched). Volume of literature is not evidence of efficacy. Run this query on PubMed.
Registered studies of LL-37 by phase and status
PhaseStudiesBreakdown
Early phase 1 1
1 completed, 0 active or recruiting, 0 stopped, 0 other
Phase 1 1
0 completed, 0 active or recruiting, 1 stopped, 0 other
Phase 2 5
4 completed, 0 active or recruiting, 0 stopped, 1 other
Phase 3 1
0 completed, 0 active or recruiting, 1 stopped, 0 other
Not applicable 2
0 completed, 0 active or recruiting, 2 stopped, 0 other
Observational 10
7 completed, 2 active or recruiting, 0 stopped, 1 other
Figure 3. 20 studies on ClinicalTrials.gov match the registry search LL-37. Multi-phase studies are counted at their highest phase. Open the full trial feed

Compare and continue

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Questions readers ask

Is LL-37 FDA-approved?

No. FDA lists 'Cathelicidin LL-37' among withdrawn compounding nominations and says it lacks sufficient safety information to know whether it would cause harm in humans4.

Does LL-37 help wounds heal?

The evidence is mixed. A 34-patient trial found faster ulcer healing at lower doses2; the larger 148-patient trial found no overall benefit3.

What is LL-37?

It is the human cathelicidin, an antimicrobial peptide that also has immunomodulatory and pro-angiogenic effects; its production is influenced by vitamin D1. PubChem lists it as a 37-residue peptide5.

What are the safety concerns with LL-37?

The ulcer trials reported it was well tolerated2,3. FDA notes immunogenicity risk and nonclinical findings of harm to male reproduction and protumorigenic effects in some tissues4.

References

Every source below was retrieved from its official API or page and cached on the data-edition date. Numbers match the margin notes.

  1. 1 PubMed Krejner A, Litwiniuk M, Grzela T. LL-37 but Not 25-Hydroxy-Vitamin D Serum Level Correlates with Healing of Venous Leg Ulcers. Arch Immunol Ther Exp (Warsz) 2017. PMID 27663530; doi:10.1007/s00005-016-0423-9.
  2. 2 PubMed Grönberg A, Mahlapuu M, Ståhle M, et al. Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial. Wound Repair Regen 2014. PMID 25041740; doi:10.1111/wrr.12211.
  3. 3 PubMed Mahlapuu M, Sidorowicz A, Mikosinski J, et al. Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial. Wound Repair Regen 2021. PMID 34687253; doi:10.1111/wrr.12977.
  4. 4 FDA Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026.
  5. 5 PubChem PubChem compound record: LL-37. C205H340N60O53 · MW 4493 g/mol.
  6. 6 PubMed Grönberg A, Zettergren L, Agren MS. Stability of the cathelicidin peptide LL-37 in a non-healing wound environment. Acta Derm Venereol 2011. PMID 21547341; doi:10.2340/00015555-1102.
  7. 7 ClinicalTrials.gov ClinicalTrials.gov registry search: LL-37. 20 registered studies at fetch.