LL-37 vs defensins vs magainin compares three of the best-known antimicrobial peptides (AMPs), natural molecules that kill bacteria, fungi and other microbes. The short answer: LL-37 is the single human cathelicidin, defensins are a large family of cysteine-rich peptides made by humans and many other species, and magainins come from frog skin.[1][4][3] All three kill microbes in the lab, but none has become an approved drug: a magainin-based cream failed its 2016 phase 3 trials, and LL-37 has reached only phase 2.[8][11]
LL-37 vs defensins vs magainin at a glance
| LL-37 | Defensins | Magainins | |
|---|---|---|---|
| Source | Humans; only human cathelicidin[1] | Humans, other animals, insects, plants[4] | Skin of the African clawed frog[3] |
| Size | 37 amino acids[1] | Usually 18 to 45 amino acids[4] | 23 amino acids[3] |
| Structure | Cut from the larger protein hCAP18[1] | Held together by disulfide bridges[4] | Amphiphilic helix on membranes (pexiganan)[6] |
| Where in the body | Skin, gut, airways, white blood cells[1] | Neutrophils, gut Paneth cells, skin and linings[5] | Not human |
| Furthest clinical step | Phase 2 wound trials[11] | Defensin mimetic brilacidin, phase 2[12] | Pexiganan, two sets of phase 3 trials[7][8] |
| Approved drug? | No | No | No[6] |
What antimicrobial peptides are
Animals and plants rely on AMPs as part of innate immunity, the fast, built-in defense that works before antibodies form. As Michael Zasloff, who discovered magainins, put it in a 2002 review, these molecules help explain why skin, eyes and seeds usually stay free of infection despite constant exposure to microbes.[17] Most AMPs are small, positively charged (cationic) molecules of 12 to 50 amino acids,[5] and pexiganan, for example, kills by punching pores in microbial membranes.[6] For background on how natural and lab-made peptides differ, see our guide to natural vs synthetic peptides.
LL-37: the human cathelicidin
LL-37 is cut from a larger protein called hCAP18 and named for its first two amino acids (two leucines) and its 37-amino-acid length. Beyond killing microbes, it neutralizes bacterial toxins, recruits immune cells and helps skin grow back over wounds.[1] Active vitamin D directly switches on its gene.[18]
It also has a downside. Abnormal LL-37 fragments drive skin inflammation in rosacea,[14] and LL-37 can bind the body’s own DNA and trigger immune cells involved in psoriasis.[15]
Defensins: a large, ancient family
Defensins are small, positively charged, cysteine-rich peptides whose shape is locked by internal disulfide bonds. In vertebrates they are grouped into alpha, beta and theta defensins.[4] In humans, alpha-defensins are mainly found in neutrophils and in Paneth cells of the small intestine, while beta-defensins are made by white blood cells and the cells lining skin and other surfaces.[5] They contribute to defense in granulocytes, the gut and the skin.[2]
Magainins: the frog-skin peptides
In 1987, Zasloff isolated two closely related 23-amino-acid peptides from the skin of the African clawed frog. At low concentrations they inhibited many bacteria and fungi without damaging red blood cells.[3] Pexiganan (MSI-78), a synthetic analog of magainin 2, became the best-studied AMP drug candidate.[6]
Evidence quality: what human trials found
Pexiganan (magainin analog)
- Earlier phase 3 trials: in two trials of 835 people with mildly infected diabetic foot ulcers, pexiganan cream performed about as well as an oral antibiotic, ofloxacin, with clinical improvement in 85% to 90%, and no significant bacterial resistance to pexiganan emerged.[7] One of the two trials did not meet its equivalence goal on its own, and the drug did not win FDA approval.[6]
- OneStep trials (2016): in 389 patients at 59 US centers, pexiganan cream failed to beat an inactive cream in both trials, with no meaningful difference in wound closure or bacterial clearance.[8]
LL-37
- 2014: in 34 people with venous leg ulcers, lower doses sped healing compared with placebo, while the highest dose did not.[10]
- 2021: a larger 148-person phase 2b trial found no significant overall benefit.[11]
Defensins
No natural defensin has completed a major therapeutic trial. Brilacidin, a non-peptide drug designed to mimic defensins, completed a 215-person phase 2 trial in serious skin infections, but it is not approved.[12] Defensins are also marketed in skincare; a 2026 review of defensin skin and hair products was written in part by an investigator and consultant for defensin product studies who holds stock in a related company.[13]
Safety and resistance
- Resistance is possible. AMPs were once thought to be nearly resistance-proof, but in a lab experiment 22 of 24 bacterial lines evolved heritable resistance to pexiganan after 600 to 700 generations.[9]
- Topical trials: LL-37 was well tolerated in its wound trials.[10][11] In the OneStep trials, overall adverse events with pexiganan were similar to the inactive cream, though bone and skin infections were higher than expected.[8]
- Unapproved products: FDA says compounded LL-37 may cause immune reactions and impurity problems and that nonclinical data suggest tumor promotion in some tissues and harm to male reproduction.[16]
Legal status and access
None of the three is an approved drug. LL-37 is sold online as a research peptide, and FDA lists it among substances with safety concerns.[16] Defensins are marketed in some skincare products as cosmetic ingredients.[13] Magainin-based pexiganan is not available as a medicine.[6]
Questions to discuss with a clinician
- For an infected wound or skin infection, which approved treatment has the best evidence?
- Do I have rosacea or psoriasis, where extra LL-37 could worsen inflammation?
- Is a product I am considering sold as a cosmetic or making drug-like claims?
The verdict
LL-37, defensins and magainins are some of nature’s most interesting antibiotics, and they shaped decades of research into new anti-infectives. As treatments, though, none has crossed the finish line: magainin’s synthetic cousin failed its final trials, LL-37 stalled at phase 2, and defensins remain mostly a lab and cosmetics story. For more on LL-37 as an immune peptide, read thymosin alpha-1 vs LL-37; for peptide fundamentals, see how to reconstitute peptides and the peptide basics hub.
This is general information, not medical advice.
