LL-37 Research, Specifications & Scientific Information

Introduction

LL-37 is not a designed molecule and not an analogue of anything. It is a peptide the human body makes: humans carry one cathelicidin gene, CAMP, whose 18 kDa precursor hCAP18 is cleaved to release a 37-residue C-terminal peptide, and the name simply records that it begins with two leucines and is 37 residues long. It sits in neutrophil granules, is induced in epithelia, kills a broad range of microbes in vitro, binds lipopolysaccharide, and modulates host cells ^{[1, 5]}.

It has also been developed further than most compounds in this library. Under the non-proprietary name ropocamptide it has been through a first-in-man study and a phase 2b trial in chronic wounds, and a separate group has run a randomised trial of a topical cream in diabetic foot ulcers. The results are mixed: a positive early trial, a larger one that did not reproduce it, and a third positive on one measure and null on the rest.

This page sets out the chemistry, the in vitro pharmacology, the animal work and those trials, with every source resolved against PubMed, Crossref or ClinicalTrials.gov when the page was built. It describes research, not use.

What Is LL-37?

LL-37 is the mature human cathelicidin peptide. The terminology around it is inconsistent in the literature and worth fixing before anything else:

• CAMP is the gene. Humans have exactly one cathelicidin gene, unlike several other mammals.
• hCAP18 is its product, an 18 kDa precursor consisting of a conserved cathelin-like prodomain and a variable C-terminal antimicrobial domain. The prodomain is not inert: it has its own antimicrobial and protease-inhibitory activity ^[4].
• LL-37 is the 37-residue peptide released from hCAP18 by proteinase 3 in neutrophils and by kallikreins in skin. Further processing in skin produces shorter fragments with different properties ^[5].
• CRAMP is the mouse cathelicidin — a different sequence. Findings from cathelicidin-deficient mice concern the system, not the human peptide.

The synthetic material supplied as a laboratory reagent is a copy of the human 37-residue free acid. Registers carry it as CAS 154947-66-7, PubChem CID 16198951 and UNII 3DD771JO2H, under the International Nonproprietary Name ropocamptide — the name under which Promore Pharma has developed it as a topical product ^[11].

It is not an approved medicine. LL-37 has not been approved by the U.S. Food and Drug Administration for any indication.

LL-37 Specifications

LL-37 is not an analogue or a designed molecule: it is a synthetic copy of a peptide the human body makes. Humans carry a single cathelicidin gene, CAMP, whose product is the 18 kDa precursor hCAP18. Proteolytic processing — by proteinase 3 in neutrophils, and by kallikreins in skin — releases the 37-residue C-terminal peptide, and the name records the first two residues and the length: two leucines, then 37 amino acids in total. The sequence above is that peptide in single-letter code, with free termini and no modification; PubChem records it as CID 16198951 with CAS registry number 154947-66-7, and the FDA/NCATS Global Substance Registration System carries it under UNII 3DD771JO2H with the International Nonproprietary Name ropocamptide. Molecular formula C205H340N60O53, average mass 4493.3 g/mol, which agrees with the mass carried in the supplier catalog. Two structural features drive nearly all the reported behaviour. The peptide is strongly cationic — six lysines and five arginines against five acidic residues — which is what draws it to the anionic surfaces of bacterial membranes and to lipopolysaccharide. And it is conformationally conditional: in dilute aqueous solution it is largely a random coil, and it folds into an amphipathic alpha-helix on contact with an anionic lipid surface. A separate register entry exists for the C-terminally amidated form, LL-37 amide, UNII 4HGQ0GC0N6, which is a different substance from the free acid described here.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does LL-37 Work?

Two mechanisms run in parallel, and the published work is clear that they are separable rather than two descriptions of one thing.

Direct antimicrobial action is physical chemistry before it is biology. The peptide carries a strong net positive charge — six lysines and five arginines against five acidic residues — and bacterial membranes and lipopolysaccharide carry a net negative one. Binding is electrostatic; the peptide then folds from a random coil into an amphipathic α-helix on the lipid surface and permeabilises the membrane ^{[1, 9]}. There is no receptor in this account, which is why resistance to it is harder for bacteria to acquire than resistance to a target-directed antibiotic, and also why its potency depends so heavily on the ionic strength of the medium.

Host-cell modulation is the second, and it is not a side effect of the first. LL-37 alters chemokine and cytokine expression in keratinocytes, and a synthetic fragment library showed that antimicrobial activity against bacterial, fungal and viral pathogens resides in specific domains of the parent peptide while the ability to stimulate interleukin-8 production does not track those domains at all. Interleukin-8 release was induced by both D- and L-amino acid forms and correlated with membrane permeability, arguing against a structure-specific receptor; it was nonetheless blocked by pertussis toxin and by an epidermal growth factor receptor kinase inhibitor, implicating receptor-associated signalling indirectly ^[5].

The practical consequence the authors drew is the one worth carrying forward: proteolytic processing in tissue may shift the balance between the two functions, so "LL-37 activity" is not a single quantity.

LL-37 Mechanism of Action

In vitro research

Antimicrobial spectrum, and the salt problem. Using radial diffusion and a standards-based broth microdilution assay, LL-37 showed minimum inhibitory concentrations below 10 µg/mL against Pseudomonas aeruginosa, Salmonella typhimurium, Escherichia coli, Listeria monocytogenes, Staphylococcus epidermidis, Staphylococcus aureus and vancomycin-resistant enterococci, even in media containing 100 mM sodium chloride. Methicillin-resistant S. aureus, Proteus mirabilis and Candida albicans were resistant in 100 mM sodium chloride but susceptible in low-salt media. Burkholderia cepacia was resistant under both conditions. The peptide was generally less potent than protegrin PG-1 ^[1].

The salt sensitivity is not a footnote. Physiological ionic strength is closer to the condition in which several organisms were resistant than to the one in which they were not, and an in vitro potency figure quoted without the salt concentration it was measured at is close to uninterpretable for this peptide.

Membrane and lipopolysaccharide interaction. LL-37 permeabilised both the outer and inner membranes of E. coli ML-35p. Chromogenic Limulus assays showed high-affinity binding to E. coli O111:B4 lipopolysaccharide with positive cooperativity (Hill coefficient 2.02). Circular dichroism showed the peptide transitioning from a random coil to an α-helix in the presence of lipid A ^[1].

Separation of antimicrobial from immunomodulatory activity. DNA microarray and confirmatory protein analysis showed LL-37 changing the expression of several chemokines and cytokines by keratinocytes, with the fragment-library dissociation described above ^[5].

Antiviral activity. LL-37 damaged the envelope of respiratory syncytial virus directly, disrupted viral particles, and decreased virus binding to and infection of human epithelial cells in vitro ^[10].

These are observations in cell-free systems and cultured cells. They establish nothing about animals or people.

What Is LL-37 Being Researched For?

Research on LL-37 divides into work on the peptide as a candidate product and work on the endogenous peptide as a marker or mediator. The two are frequently cited as though they were one body of evidence, and they are not.

As a candidate topical product:

• Hard-to-heal venous leg ulcers — a first-in-man study and a phase 2b trial ^{[7, 11]}.
• Diabetic foot ulcer with mild infection — a randomised double-blind trial of a cream formulation ^{[12, 14]}.

As an endogenous molecule:

• Atopic dermatitis and psoriasis — comparative expression in lesional skin ^[3].
• Mycobacterial host defence and vitamin D — the vitamin D response element in the CAMP gene and its consequences ^{[6, 8]}.
• Antiviral host defence — respiratory syncytial virus ^[10].
• Cutaneous host defence generally — the cathelicidin-deficient mouse work and the reviews built on it ^{[2, 13]}.

Human Research on LL-37

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

First-in-man, venous leg ulcers

Population. 34 participants with hard-to-heal venous leg ulcers ^[7].

Endpoint and design. Safety and the relationship between concentration and effect. A three-week open-label run-in on placebo, then a four-week randomised double-blind phase with twice-weekly topical applications of LL-37 at 0.5, 1.6 or 3.2 mg/mL or placebo, then four weeks of follow-up ^[7].

Result. Closure-rate constants for 0.5 and 1.6 mg/mL were approximately six-fold and three-fold higher than placebo (p = 0.003 and p = 0.088 respectively). Square-root transformed wound-area data showed improvement for both of those groups against pre-treatment values (p < 0.001 and p = 0.011). Mean ulcer area decreased by 68% in the 0.5 mg/mL group and 50% in the 1.6 mg/mL group. No difference was observed between the 3.2 mg/mL group and placebo. There were no local or systemic safety concerns ^[7].

Limitations. 34 participants, four weeks of treatment, and a non-monotonic pattern in which the highest concentration behaved like placebo. Non-monotonic results are common in small trials and are as easily explained by noise as by biology.

Phase 2b, venous leg ulcers (HEAL LL-37)

Population. 148 patients with hard-to-heal venous leg ulcers; mean age 67.6 years, median ulcer duration 20.3 months, mean wound size at randomisation 11.6 cm² ^[11].

Endpoint and design. A double-blind, randomised, placebo-controlled phase 2b trial of topical LL-37 at 0.5 or 1.6 mg/mL, or placebo, in combination with compression therapy ^[11].

Result. The efficacy analysis in the full study population identified no significant improvement with LL-37 against placebo. A post hoc analysis reported statistically significant improvement in several interrelated parameters within the subgroup whose target wound was at least 10 cm² at randomisation. The study drug was well tolerated and safe at both concentrations ^[11].

Limitations. This is the largest and most rigorous trial of the compound, and its primary analysis was negative. The subgroup finding is post hoc — generated after the data were seen, in a subgroup defined by a known prognostic factor — and the authors themselves describe it as warranting a further, adequately powered study rather than as a result. A page that reported the 2014 trial without this one would be misleading.

Diabetic foot ulcer with mild infection

Population. Participants with diabetic foot ulcer and mild infection, recruited in Jakarta between January 2020 and June 2021 ^{[12, 14]}.

Endpoint and design. Randomised, double-blind, placebo-controlled. LL-37 cream or placebo cream applied twice weekly for four weeks, with wounds measured at days 7, 14, 21 and 28 and processed by image analysis; LL-37, IL-1α and TNF-α in wound fluid measured by ELISA; aerobic bacterial colonisation counted from culture isolates ^[12].

Result. Baseline LL-37 concentrations in the ulcers were low and comparable between groups — 1.07 ng/mg protein (range 0.37–4.96) in the LL-37 group and 1.11 (0.24–2.09) in the placebo group. The increase in granulation index was consistently greater in the LL-37 group at days 7, 14, 21 and 28 (p = 0.031, 0.009, 0.006 and 0.037). IL-1α and TNF-α rose in both groups at days 14 and 21 with no significant difference, and the reduction in aerobic bacterial colonisation did not differ significantly between groups at any time point ^[12].

Limitations. A single-country trial with one positive morphological measure and null results on both of the mechanistic measures it set out to test. That an antimicrobial peptide applied to an infected ulcer did not significantly reduce bacterial colonisation is a finding in its own right, and it sits awkwardly beside the in vitro antimicrobial data.

Observational and biomarker research

Expression of LL-37 and human β-defensin 2 was compared in skin-biopsy specimens from patients with psoriasis, patients with atopic dermatitis and normal subjects, by immunohistochemistry, immunodot and Western blot, and quantitative RT-PCR. Both peptides were abundant in the superficial epidermis in psoriasis and significantly decreased in acute and chronic atopic dermatitis lesions (p = 0.006 and p = 0.03); mRNA followed the same pattern (p = 0.02 for LL-37). In a colony-forming assay, the combination of the two peptides killed S. aureus synergistically ^[3].

A cross-sectional study has examined serum 25-hydroxyvitamin D, LL-37 and vitamin D pathway polymorphisms together in a Canadian First Nation population with endemic tuberculosis ^[8], and higher nasal LL-37 concentrations were associated with protection in a healthy adult respiratory syncytial virus challenge model ^[10].

Limitations. These are observational comparisons of naturally occurring concentrations. They describe associations between a measurement and a condition, in populations; they do not establish that administering the peptide changes anything.

Preclinical Research on LL-37

Animal research

Cathelicidin-deficient mice. Combining mouse and bacterial genetics in a model of cutaneous infection, cathelicidins were shown to be an important native component of innate host defence in mice, providing protection against necrotic skin infection caused by Group A Streptococcus ^[2].

The precision point: the mouse peptide is CRAMP, encoded by a similar gene to the human one with comparable antimicrobial spectrum and tissue distribution, but it is not LL-37. This experiment establishes that the cathelicidin system matters in mice. It does not establish what administering human LL-37 does.

Exogenous LL-37 in a viral model. In a murine model of pulmonary respiratory syncytial virus infection, exogenously applied LL-37 was protective against disease, with maximal effect when applied at the same time as the virus. Endogenous murine cathelicidin, induced by infection, also had a role in protection ^[10].

This is the clearer of the two for the compound as such, because the human peptide was administered rather than inferred — and the timing dependence is worth noting, since an intervention that works only when given concurrently with an exposure is a different kind of intervention from one given after it.

Limitations. The animal literature on administered LL-37 is thin next to the in vitro literature, which is unusual for a compound that has reached phase 2b. Findings described in this section were observed in animals, and nothing in them establishes anything about humans.

Other Areas of LL-37 Research

In vitro research

The prodomain. hCAP18 is usually treated as an inactive carrier for LL-37, and it is not: the cathelin-like prosequence has its own antimicrobial activity and inhibits proteases ^[4]. A preparation of "LL-37" is the mature peptide only, and does not reproduce whatever the precursor contributes in tissue.

Processing and fragments. In skin, LL-37 is further cleaved into shorter peptides with different balances of antimicrobial and immunostimulatory activity ^[5]. This is the mechanistic basis of the cathelicidin hypothesis in rosacea, where abnormal processing rather than abnormal quantity is the proposed problem, and it means that the peptide's activity in tissue is a function of the local protease environment as much as of how much peptide is present.

Double-edged biology. The same properties that make cathelicidins useful in host defence make them plausible contributors to inflammatory disease, and the review literature on clinical translation treats that duality as the central obstacle rather than as a caveat ^[13]. A compound that is elevated in psoriasis and reduced in atopic dermatitis ^[3] is not straightforwardly good or bad to have more of.

Membrane biophysics. The structural literature describes LL-37 as a pore-forming peptide and as a host-cell modulator in the same breath, and the reviews of it are explicit that the two functions are difficult to separate in a formulation ^[9].

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

LL-37 vs Related Compounds

Composition and mechanism only; no comparison of effect is made between these compounds.

Origin

LL-37 — a human peptide, released from the single human cathelicidin precursor hCAP18. KPV — a three-residue fragment of a human hormone. Thymosin α1 — a 28-residue human peptide from prothymosin α. BPC-157 — a synthetic peptide whose stated origin is a gastric juice fraction.

Mode of action

LL-37 — electrostatic binding to anionic membranes and lipopolysaccharide, with a coil-to-helix transition on contact ^[1]. KPV — uptake by the PepT1 transporter, then inhibition of NF-κB signalling. Thymosin α1 — immunomodulation reported through Toll-like receptor signalling in dendritic cells. BPC-157 — no identified target.

Direct antimicrobial activity

LL-37 — yes, broad-spectrum in vitro, salt-dependent ^[1]. KPV — reported against Staphylococcus aureus and Candida albicans in vitro. Thymosin α1 and BPC-157 — not characterised as direct antimicrobials.

Clinical position

LL-37 — published randomised trials including a negative phase 2b ^[11]. Thymosin α1 — an approved pharmaceutical product in a number of countries. KPV and BPC-157 — no published controlled trial. None of the four is an approved medicine in the United States, and approval is specific to a compound and an indication.

Chemical & Molecular Characteristics

LL-37 is a linear 37-residue peptide of standard L-amino acids with free termini: LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES. Molecular formula C205H340N60O53, average mass 4493.3 g/mol, PubChem CID 16198951, CAS 154947-66-7, UNII 3DD771JO2H.

Charge is the structure. Count the ionisable side chains: six lysines and five arginines positive, three aspartates and two glutamates negative, giving a strong net positive charge at physiological pH. That charge is not decoration — it is the binding mechanism, and it is why activity falls as ionic strength rises ^[1].

Conformation is conditional. In dilute aqueous buffer the peptide is largely disordered. On contact with an anionic lipid surface it adopts an amphipathic α-helix, with hydrophobic residues on one face and cationic residues on the other ^{[1, 9]}. A circular dichroism spectrum of this peptide is therefore a statement about the solvent as much as about the molecule, and a specification that reports secondary structure without reporting the conditions reports very little.

The amide is a different substance. The FDA/NCATS register carries a separate entry, LL-37 amide, under UNII 4HGQ0GC0N6. C-terminal amidation removes a negative charge and raises the net positive charge, which for a peptide whose mechanism is electrostatic is not a trivial modification. The free acid described above is what the identifiers on this page refer to; a certificate of analysis showing a mass one dalton below 4493.3 is describing the amide.

Aggregation and adsorption. Highly cationic amphipathic peptides adsorb to glass and to plastic and self-associate at higher concentrations, which is a recognised source of discrepancy between nominal and actual concentrations in antimicrobial assays. This is a handling characteristic rather than a property of the molecule, and it is one reason published minimum inhibitory concentrations for this peptide vary between laboratories even when the salt concentration is stated.

Analytical Specifications

Analytical figures are lot-specific. Fields the catalog does not carry for the current lot are omitted rather than filled with a typical value. The certificate of analysis and the safety data sheet for the exact lot supplied are provided with a laboratory order; no purity figure on this page is a substitute for that document.

Frequently Asked Questions

Scientific References

1. Turner J, Cho Y, Dinh NN, et al.. Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils Antimicrobial agents and chemotherapy; 1998. PMID 9736536 doi:10.1128/AAC.42.9.2206
2. Nizet V, Ohtake T, Lauth X, et al.. Innate antimicrobial peptide protects the skin from invasive bacterial infection Nature; 2001. PMID 11719807 doi:10.1038/35106587
3. Ong PY, Ohtake T, Brandt C, et al.. Endogenous antimicrobial peptides and skin infections in atopic dermatitis The New England journal of medicine; 2002. PMID 12374875 doi:10.1056/NEJMoa021481
4. Zaiou M, Nizet V, Gallo RL. Antimicrobial and protease inhibitory functions of the human cathelicidin (hCAP18/LL-37) prosequence The Journal of investigative dermatology; 2003. PMID 12713586 doi:10.1046/j.1523-1747.2003.12132.x
5. Braff MH, Hawkins MA, Di Nardo A, et al.. Structure-function relationships among human cathelicidin peptides: dissociation of antimicrobial properties from host immunostimulatory activities Journal of immunology (Baltimore, Md. : 1950); 2005. PMID 15778390 doi:10.4049/jimmunol.174.7.4271
6. Martineau AR, Wilkinson KA, Newton SM, et al.. IFN-gamma- and TNF-independent vitamin D-inducible human suppression of mycobacteria: the role of cathelicidin LL-37 Journal of immunology (Baltimore, Md. : 1950); 2007. PMID 17513768 doi:10.4049/jimmunol.178.11.7190
7. 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 and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society; 2014. PMID 25041740 doi:10.1111/wrr.12211
8. Larcombe L, Mookherjee N, Slater J, et al.. Vitamin D, serum 25(OH)D, LL-37 and polymorphisms in a Canadian First Nation population with endemic tuberculosis International journal of circumpolar health; 2015. PMID 26294193 doi:10.3402/ijch.v74.28952
9. Xhindoli D, Pacor S, Benincasa M, et al.. The human cathelicidin LL-37--A pore-forming antibacterial peptide and host-cell modulator Biochimica et biophysica acta; 2016. PMID 26556394 doi:10.1016/j.bbamem.2015.11.003
10. Currie SM, Gwyer Findlay E, McFarlane AJ, et al.. Cathelicidins Have Direct Antiviral Activity against Respiratory Syncytial Virus In Vitro and Protective Function In Vivo in Mice and Humans Journal of immunology (Baltimore, Md. : 1950); 2016. PMID 26873992 doi:10.4049/jimmunol.1502478
11. 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 and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society; 2021. PMID 34687253 doi:10.1111/wrr.12977
12. Miranda E, Bramono K, Yunir E, et al.. Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial Archives of dermatological research; 2023. PMID 37480520 doi:10.1007/s00403-023-02657-8
13. Dzurová L, Holásková E, Pospíšilová H, et al.. Cathelicidins: Opportunities and Challenges in Skin Therapeutics and Clinical Translation Antibiotics (Basel, Switzerland); 2024. PMID 39858288 doi:10.3390/antibiotics14010001
14. Efficacy of LL-37 Cream on Bacteria Colonization, Inflammation Response and Healing Rate of Diabetic Foot Ulcers 2019. NCT04098562

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Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.

Related laboratory reagent: LL-37 specifications and lot documentation