LL-37

LL-37 is the only cathelicidin-family antimicrobial peptide made by the human body. It is a 37-amino-acid fragment cut from a larger precursor protein (hCAP-18) and released by white blood cells and skin, gut, and lung cells as part of the innate immune system. It kills a broad range of bacteria and some viruses and fungi by disrupting their outer membranes, and it also signals to immune cells and helps coordinate wound healing. It is studied as a natural antimicrobial and tissue-repair peptide, not as an approved drug.

Research snapshot

Category	Current information
Peptide category	Endogenous host-defense (cathelicidin) peptide
Primary research interest	Antimicrobial activity, immune signaling, and wound healing
Highest available evidence	Published human clinical trials of topical LL-37 for venous leg ulcers (a 34-patient randomized phase I/II in 2014 and a 148-patient phase IIb in 2021, which missed its primary result), plus a small phase 1/2 melanoma injection study
Human research available	Yes, but narrow: topical LL-37 for leg ulcers and a four-patient intratumoral melanoma study. No oral or subcutaneous injection trials were identified, and most other human data are observational (natural LL-37 levels)
Development status	Investigational research compound (DrugBank development name “ropocamptide”); not an approved medicine
Regulatory status	Not FDA-approved. Not in any FDA interim category on the May 14, 2026 list; FDA lists it among withdrawn nominations. Advisory committee review is reported by a law-firm summary, not confirmed on FDA pages

Peptide category: endogenous host-defense (cathelicidin) peptide. Primary research interest: antimicrobial activity, immune signaling, and wound healing. Highest available evidence: published human clinical trials of topical LL-37 for venous leg ulcers, plus a small melanoma injection study. Human research available: yes, but narrow, and no oral or subcutaneous injection trials were identified. Development status: investigational (DrugBank development name “ropocamptide”), not an approved medicine. Regulatory status: not FDA-approved, and under review for the compounding bulks list.

Technical identity

Technical property	Information
Primary name	LL-37
Alternative names	hCAP-18 (109-135) fragment, cathelicidin antimicrobial peptide, ropocamptide (DrugBank development identifier), CAMP gene product
Peptide sequence	LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES (37 amino acids, free-acid C-terminus as isolated natively)
Amino-acid length	37 residues
Molecular formula	C205H340N60O53
Molecular weight	Approximately 4,493.3-4,493.6 Da (native free-acid form; sources vary slightly in the decimal, consistent with rounding, not a different molecule)
CAS Registry Number	154947-66-7 (native free-acid form, per AnaSpec, consistent with the PubChem-matched formula). A separate number, 597562-32-8, is also widely listed online but corresponds to the C-terminally amidated derivative (“LL-37 amide”) per BOC Sciences, a genuine, unresolved conflict; see the note below.
PubChem CID	16198951
Chemical modifications	Native, unmodified free-acid peptide; a distinct C-terminally amidated derivative also circulates commercially under an overlapping CAS number (see caveat)
Peptide class	Cathelicidin, amphipathic alpha-helical antimicrobial peptide
Primary biological target	Bacterial/fungal/viral membranes (direct lytic action) and multiple human receptors including formyl peptide receptor 2 (FPR2/ALX), P2X7, and EGFR-transactivation pathways
Developer or originator	Naturally occurring human peptide; not developed by a single company, though multiple peptide-synthesis vendors produce synthetic versions for research
Development status	Investigational/research use only (DrugBank DB16532, UNII 3DD771JO2H)

Primary name: LL-37. Alternative/development names: hCAP-18 (109-135) fragment, cathelicidin antimicrobial peptide, ropocamptide (DrugBank development identifier), CAMP gene product. Peptide sequence: LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES (37 amino acids, free-acid C-terminus as isolated natively). Molecular formula: C205H340N60O53. Molecular weight: approximately 4,493.3-4,493.6 Da (sources vary slightly in the decimal, consistent with rounding, not a different molecule). PubChem CID: 16198951 (formula matches C205H340N60O53). UNII: 3DD771JO2H (DrugBank, listed under “ropocamptide”). DrugBank ID: DB16532. Peptide class: cathelicidin, amphipathic alpha-helical antimicrobial peptide. Primary biological target: bacterial/fungal/viral membranes (direct lytic action) and multiple human receptors including formyl peptide receptor 2 (FPR2/ALX), P2X7, and EGFR-transactivation pathways involved in chemotaxis and wound repair. Developer/originator: naturally occurring human peptide; not developed by a single company, though Araim, and multiple peptide synthesis vendors, produce synthetic versions for research. Development status: investigational/research use only.

A genuine CAS-number conflict exists across commercial sources and is flagged rather than resolved by picking one number. Peptide vendor AnaSpec (and several other synthesis suppliers) list CAS 154947-66-7 for native, C-terminal free-acid LL-37 with the formula C205H340N60O53 that matches PubChem CID 16198951. Other vendors, including peptide.com and GlpBio, list the number 597562-32-8 for a product simply labeled “LL-37, Antimicrobial Peptide, human”, but BOC Sciences lists that same CAS number, 597562-32-8, explicitly for “LL-37 amide,” a C-terminally amidated variant, which is a chemically distinct molecule from the native, non-amidated peptide isolated from human tissue. This means some commercial listings appear to attach the amide-form CAS number to product pages that do not disclose amidation. Readers and researchers should treat 154947-66-7 as the number associated with native, free-acid LL-37 (consistent with the PubChem-matched formula) and treat 597562-32-8 as specific to the amidated derivative, not as an interchangeable synonym.

What is LL-37?

LL-37 gets its name from its first two amino acids (leucine-leucine) and its 37-residue length. It is produced when the enzyme proteinase 3 cleaves the C-terminal end off a larger, inactive precursor protein called hCAP-18, which is stored in the granules of neutrophils (a type of white blood cell) and also made by skin keratinocytes, epithelial cells lining the airway and gut, and other tissues. It belongs to a peptide family called cathelicidins, found across many mammals, but LL-37 is the only cathelicidin peptide humans produce.

It is naturally occurring, not synthetic or engineered, though laboratories synthesize identical or modified copies for research. It was first isolated and characterized from human neutrophils and bone marrow in the 1990s, and has since become one of the most heavily studied human antimicrobial peptides, with hundreds of published papers on its structure, antimicrobial spectrum, and immune signaling roles.

Researchers are interested in LL-37 for several reasons. First, it kills a wide range of bacteria (including some antibiotic-resistant strains), certain fungi, and has activity against some enveloped viruses, making it a candidate template for new anti-infective strategies at a time when antibiotic resistance is a major public health concern. Second, it does more than kill microbes directly, it also acts as a signaling molecule, attracting immune cells to sites of infection or injury, promoting angiogenesis (new blood vessel growth), and accelerating re-epithelialization in wound healing. Third, LL-37 has a well-documented dark side: when overexpressed or dysregulated, it is implicated in inflammatory skin diseases such as psoriasis and rosacea, and it has been studied in contexts of autoimmune activation, making it a double-edged molecule whose effects depend heavily on concentration and tissue context.

LL-37 has no approved pharmaceutical use as a standalone drug. Development interest has focused on derivative fragments and structural analogs designed to retain antimicrobial or wound-healing activity while reducing toxicity or improving stability, rather than administering full-length native LL-37 itself as a therapeutic.

How does it work?

Plain-English explanation

LL-37 is shaped like a flexible rod that folds into a coiled, amphipathic (part water-loving, part fat-loving) helix when it meets a membrane. Because bacterial cell membranes carry a different electrical charge and composition than human cell membranes, LL-37 preferentially inserts into and punches holes in bacterial membranes, causing their contents to leak out and the microbe to die. Separately, small amounts of LL-37 act more like a hormone or messenger: they tell nearby immune cells to move toward the area, ramp up inflammation when needed, and support the tissue-repair process after an injury.

Technical explanation

LL-37 exerts direct antimicrobial action largely through a “carpet” or “toroidal pore” mechanism: it adsorbs onto anionic phospholipid-rich microbial membranes, aggregates, and disrupts membrane integrity, causing lysis. Beyond direct lysis, LL-37 engages multiple host-cell receptors, including formyl peptide receptor 2 (FPR2/ALX), which mediates chemotaxis of monocytes, neutrophils, and T cells; P2X7 purinergic receptors, implicated in inflammasome activation; and transactivation of the epidermal growth factor receptor (EGFR), which contributes to keratinocyte migration and re-epithelialization during wound healing. LL-37 also binds and neutralizes bacterial lipopolysaccharide (LPS) and lipoteichoic acid, modulating downstream Toll-like receptor signaling and reducing excessive inflammatory cytokine release in some contexts. Its cationic, amphipathic alpha-helical structure (net charge of approximately +6) underlies both its membrane-selective antimicrobial activity and its receptor-binding promiscuity.

Potential benefits and research applications

Broad-spectrum antimicrobial activity

What is being investigated: whether LL-37 or LL-37-derived fragments can kill or inhibit bacteria (including multidrug-resistant strains), fungi, and some enveloped viruses. How the effect might occur: direct membrane disruption plus neutralization of bacterial endotoxin. Evidence: extensive published laboratory (in vitro) research and some animal-infection models; human evidence is limited to observational studies correlating natural LL-37 levels with infection outcomes, not interventional dosing trials of purified LL-37 as a treatment. Strength: strong laboratory/mechanistic evidence (Tier 4), limited direct human interventional evidence. Limitation: LL-37 is rapidly degraded by host and microbial proteases and can be cytotoxic to human cells at higher concentrations, which has so far limited its direct clinical development as an injectable or systemic antimicrobial.

Wound healing and tissue repair

What is being investigated: whether LL-37 accelerates wound closure by promoting keratinocyte migration, angiogenesis, and immune cell recruitment. How the effect might occur: EGFR transactivation and FPR2-mediated chemotaxis, as described above. Evidence: laboratory and animal wound-healing models, human observational studies noting reduced LL-37 in chronic non-healing wounds, and two randomized human trials of a topical LL-37 gel in venous leg ulcers. Strength: Tier 1 (small, mixed human trials) with Tier 3-4 animal and mechanistic support. The 2014 trial (34 patients) reported faster healing at 0.5 and 1.6 mg/mL, but the 2021 phase IIb trial (about 148 patients) found no significant improvement overall, with a benefit seen only in a post hoc subgroup of large ulcers. Limitation: results are mixed, both papers have company-affiliated authors, and no trial of systemic or injected LL-37 for wound healing was identified.

Immune modulation and inflammatory disease

What is being investigated: LL-37’s dual role as both a protective immune signal and a driver of pathological inflammation. How the effect might occur: at physiologic levels it aids chemotaxis and antimicrobial defense; at pathologically elevated levels (as seen in psoriatic skin) it complexes with self-DNA/RNA and can trigger autoinflammatory signaling through plasmacytoid dendritic cells. Evidence: human observational research directly links elevated LL-37 expression to psoriasis and rosacea skin lesions. Strength: Tier 2 human observational evidence for the association; the peptide is a research target for inhibition (not supplementation) in these disease contexts. Limitation: this benefit/risk duality means “more LL-37” is not uniformly beneficial, and community claims that supplementing LL-37 broadly “boosts immunity” are not supported by controlled human evidence.

What dosage information circulates?

Figures in this section summarize amounts and schedules reported in published research or circulating online. Their inclusion documents what is reported and does not establish that a regimen is verified, safe, effective, or appropriate.

Reported use or research objective	Route reported	Amount reported	Frequency reported	Reported duration	Evidence or source category
Venous leg ulcers (first-in-man phase I/II, 34 patients)	Topical, applied to the ulcer	0.5, 1.6, or 3.2 mg/mL solution	Twice weekly	4 weeks randomized, after a 3-week placebo run-in	Published human clinical trial (Grönberg 2014)
Venous leg ulcers (phase IIb, about 148 patients)	Topical, 25 µL per cm² of ulcer	0.5 or 1.6 mg/mL (12.5 or 40 µg per cm²)	Twice weekly	Up to 13 weeks, after a 3-week run-in	Published human clinical trial (Mahlapuu 2021)
Metastatic melanoma skin lesions (phase 1/2, 4 patients enrolled)	Injected into tumors	Dose levels not published in the registry record	Once weekly into 2 to 4 tumors	Up to 8 weeks	Registered human trial, completed (NCT02225366), plus one case report
Any other human use (oral, subcutaneous, systemic)	Not applicable	No established or reliably sourced dosing information was identified	Not applicable	Not applicable	None identified
Wound-healing / anti-infective models	Topical or local injection	Microgram-to-milligram-per-kilogram ranges	Varies by study	Varies by study	Published animal research (mouse and other models)
General “research compound” framing	Not consistently reported	Community/vendor dosing figures circulate but could not be traced to an identifiable original source	Not established	Not established	Community / vendor reported, unverified

Amounts studied in human research

Research objective	Amount studied	Frequency	Duration	Route	Study population	Source
Safety and dose response, venous leg ulcers	0.5, 1.6, 3.2 mg/mL (applied volume not stated in the abstract)	Twice weekly	4-week randomized phase, 3-week placebo run-in, 4-week follow-up	Topical	34 adults with hard-to-heal venous leg ulcers	Grönberg 2014, randomized placebo-controlled trial
Efficacy and safety, venous leg ulcers	0.5 or 1.6 mg/mL, 25 µL per cm² (12.5 or 40 µg per cm²)	Twice weekly (every 3 ± 1 days)	13-week treatment, 3-week run-in, 16-week follow-up	Topical, in a PVA gel vehicle	About 148 adults with hard-to-heal venous leg ulcers	Mahlapuu 2021, phase IIb (HEAL LL-37)
Dose finding and immune response, melanoma	Dose levels not published in the registry record (up to 4 levels planned)	Once weekly into 2 to 4 tumors	Up to 8 weeks	Intratumoral injection	4 patients enrolled (up to 36 planned), stage III/IV melanoma with skin lesions	ClinicalTrials.gov NCT02225366

The wound-healing studies are the best human evidence for administered LL-37, and they are mixed. In the 2014 first-in-man trial, the 0.5 mg/mL group healed about six times faster than placebo (p = 0.003) and the 1.6 mg/mL group about three times faster (p = 0.088, short of the usual significance cutoff), while the highest strength, 3.2 mg/mL, did no better than placebo. The authors reported no local or systemic safety concerns. According to PubMed, this trial is at DOI 10.1111/wrr.12211.

The 2021 phase IIb trial was larger and tested the two lower strengths for up to 13 weeks. It found no significant improvement in healing across the whole group. A post hoc look at patients whose ulcers were at least 10 cm² showed better healing parameters with LL-37, but post hoc subgroup findings are hypothesis-generating, not proof. The gel was well tolerated, and the serious adverse events reported were not judged related to the drug. Both papers have authors affiliated with the company developing the product (DOI 10.1111/wrr.12977).

The melanoma study (NCT02225366, M.D. Anderson, completed 2020) injected LL-37 into skin tumors weekly for up to eight weeks. The registry lists only 4 enrolled patients against a plan of up to 36, and no results paper was identified. A single published case report describes one patient whose injected lesions shrank, but who developed widespread wart-like and blistering skin lesions that cleared within two months after injections stopped (DOI 10.1111/cup.13262).

Important unit note: these are concentrations of a gel or solution applied to a wound, not milligram amounts per injection. They cannot be converted into an injectable or oral amount, and no oral, subcutaneous, or systemic human dosing study was identified.

Amounts studied in animal research

Preclinical studies in mice and other animal models have applied synthetic LL-37 topically or by local injection at microgram-to-milligram-per-kilogram ranges for wound-healing and anti-infective models, but exact amounts vary considerably by study design, delivery vehicle, and research objective, and no single “standard” animal dose has emerged across the literature. Because these are laboratory research doses in animals, they should not be treated as a basis for any human amount.

Practitioner and community-reported protocols

LL-37 is sold by research-peptide vendors and is occasionally discussed in online peptide communities in the context of injected or topical use for wound healing or general immune support, sometimes citing amounts in the low-milligram range. Widely repeated online, but its original source could not be verified. These reports are community/vendor-reported (Tier 6), are not tied to any published human dosing study, and do not distinguish the native free-acid form from the amidated variant discussed in the Technical Identity section above, which is itself a source of confusion in circulating protocols.

Side effects, risks, and limitations

In the topical leg-ulcer trials, LL-37 gels were reported as well tolerated, with no local or systemic safety concerns in the 2014 trial and no drug-related serious adverse events in the 2021 trial. That safety record applies only to topical use on wounds. Injection into tumors produced a reported case of widespread skin toxicity that resolved after stopping, and there is no controlled human safety data for systemic or subcutaneous use. Laboratory research indicates LL-37 can be cytotoxic (membrane-disrupting) to human cells, including red blood cells, at higher concentrations, similar to its mechanism against microbial membranes, a key reason it has not advanced as a direct injectable therapeutic. Its dual role in inflammatory skin disease means research groups are also investigating LL-37 inhibitors, not just supplementation, further underscoring that “more LL-37” is not inherently safe or beneficial. Products marketed by research-chemical or peptide vendors carry the general risks associated with unregulated research compounds: unverified purity and identity, possible mislabeling of the native versus amidated form (see the CAS conflict above), inconsistent concentration, and no sterility assurance for any material not manufactured under pharmaceutical-grade controls.

Regulatory and developmental status

LL-37 itself is not an approved drug in any jurisdiction identified. It is an endogenous human peptide that has been tested in topical wound-healing trials and a small melanoma injection study by the company developing it, and DrugBank lists it under the development name “ropocamptide” as investigational. No phase III result or marketing application was identified. On the compounding side, FDA’s Category 2 list (substances with significant safety concerns) once included LL-37, and a legal summary of the July 2026 advisory committee meeting reports that on April 15, 2026 HHS confirmed LL-37 was removed from Category 2 because its nominators withdrew the nominations. FDA’s own pages do not give that date: its 503A categories list (updated May 14, 2026) shows LL-37 in no category, and its safety-risk page lists it among withdrawn nominations, citing immunogenicity risk and nonclinical findings of detrimental effects on male reproduction and possible tumor promotion in some tissues. Withdrawal is not a clearance. Removal does not make it permitted: it does not place LL-37 on the 503A bulks list, and the same summary says the compounding advisory committee will consider LL-37 at a meeting before the end of February 2027. LL-37 is also sold by suppliers labeled “for research use only, not for human or veterinary use.”

Frequently asked questions

What is LL-37?

LL-37 is the only cathelicidin antimicrobial peptide made naturally by the human body, released from immune and epithelial cells to fight infection and support wound healing.

How does LL-37 work?

It punches holes in microbial membranes to kill them directly, and it also signals to immune cells and skin cells to coordinate inflammation control and tissue repair.

What dosage has been studied for LL-37?

Published human trials used LL-37 as a topical gel for venous leg ulcers: 0.5, 1.6, or 3.2 mg/mL twice weekly in a 34-patient trial, and 0.5 or 1.6 mg/mL twice weekly for up to 13 weeks in a phase IIb trial. A small melanoma study injected it into tumors weekly. No established or reliably sourced dosing information was identified for oral or subcutaneous use.

What dosage commonly circulates online for LL-37?

Some peptide-community and vendor sources mention low-milligram topical or injected amounts, but these figures are community/vendor-reported and their original source could not be verified.

Is LL-37’s CAS number 154947-66-7 or 597562-32-8?

Both numbers appear online, but they most likely refer to different molecules: 154947-66-7 is associated with the native, free-acid form matching PubChem’s listed formula, while 597562-32-8 is explicitly labeled by at least one supplier as the C-terminally amidated form (“LL-37 amide”). Some vendor listings appear to apply the amide-form number to unlabeled “LL-37” products.

Has LL-37 been studied in humans?

Yes. Beyond observational studies of natural LL-37 levels, two randomized trials tested a topical LL-37 gel in venous leg ulcers (2014 and 2021) and a small phase 1/2 study injected it into melanoma lesions. The larger 2021 trial did not show a significant benefit overall.

What side effects have been reported for LL-37?

Topical LL-37 was reported as well tolerated in the leg-ulcer trials. Injection into melanoma lesions was linked in one case report to widespread skin lesions that cleared after stopping. Laboratory work shows LL-37 can damage human cell membranes at higher concentrations, and there is no controlled safety data for systemic use.

Is LL-37 approved as a medicine?

No. It is not approved as a drug by FDA or any major regulator identified. It was removed from FDA’s Category 2 compounding list in April 2026 after its nominations were withdrawn, and the compounding advisory committee is slated to consider it before the end of February 2027.

What remains unknown about LL-37?

Whether purified LL-37 can be safely and effectively dosed as a therapeutic (versus its natural endogenous role), how to reconcile its protective and pro-inflammatory effects at different concentrations, and which CAS-numbered commercial product researchers are actually receiving remain open, practically important questions.

Bottom line

LL-37 is a well-characterized, naturally occurring human antimicrobial and immune-signaling peptide with a large body of laboratory and observational evidence behind its biology. The strongest evidence for administered LL-37 is two randomized trials of a topical gel in venous leg ulcers: a 34-patient trial in 2014 with encouraging results at 0.5 and 1.6 mg/mL, and a 148-patient phase IIb trial in 2021 that did not show a significant benefit overall, with only a post hoc signal in large ulcers. A small melanoma injection study enrolled 4 patients and published no results paper. No oral or subcutaneous dosing study was identified, and circulating community dosing figures are unverified. Practical issue for anyone looking at commercial material: the CAS-number conflict between native LL-37 (154947-66-7) and an amidated derivative sold under the same name (597562-32-8) matters chemically and is not always disclosed. LL-37 is not approved as a drug, left FDA’s Category 2 list in April 2026, and is slated for compounding advisory committee review before the end of February 2027.