Pexiganan

MSI-78, Locilex (pexiganan acetate cream 0.8%); an analogue of magainin 2 from the African clawed frog

Antimicrobial & antiviral

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

1What it is

Pexiganan is a synthetic antimicrobial peptide based on magainin 2, a germ-killing peptide found in the skin of the African clawed frog (Xenopus laevis). It was one of the first antimicrobial peptides developed as a drug, formulated as a topical cream (Locilex) for mild infections of diabetic foot ulcers. Its story is a cautionary one: despite a sound mechanism and good laboratory activity, it twice failed to win approval.

It is not a community self-use peptide — it is a topical anti-infective that did not reach market. People find it here because it is a textbook example of the gap between antimicrobial-peptide promise and clinical results.

2How it's thought to work

Pexiganan is a short, positively charged peptide that folds into an α-helix on contact with a bacterial membrane. Its charged and greasy faces let it carpet and then permeabilise the membrane, killing the bacterium quickly. Because the target is the membrane's basic physical makeup rather than a specific protein, it works against a broad range of Gram-positive and Gram-negative bacteria and selects for resistance only slowly in the lab — the main reason it was so attractive.

A synthetic magainin from frog skin, applied topically to diabetic foot infection. It lyses bacteria on contact; trials matched but did not beat oral antibiotics.Schematic — not to scale

3What the research shows

Graded A (negative)

Diabetic foot ulcer infection

In the 1990s, trials compared topical pexiganan against oral ofloxacin for infected diabetic foot ulcers; pexiganan was roughly comparable, but because it was tested against an active antibiotic rather than placebo, the FDA did not approve it (an advisory committee declined in 1999). The compound was revived by Dipexium and tested in two large, randomised, double-blind, vehicle-controlled Phase 3 trials, OneStep-1 and OneStep-2, in mild diabetic foot infection. Topline results in 2016 showed pexiganan cream did not beat the vehicle (placebo) cream on the primary clinical-response endpoint in either trial, and did not improve bacterial eradication; osteomyelitis and cellulitis were somewhat higher than expected in the pexiganan arms. The programme failed and the company's value collapsed. This is the clearest high-quality human data and it is negative.

Graded C/D

Resistance and spectrum

Laboratory work consistently shows broad activity and slow resistance selection — the promise that the clinical trials did not convert into benefit, probably because topical peptide plus good wound care did not add to wound care alone.

4Reported side effects and interactions

Literature-reported

Topical pexiganan was generally well tolerated locally; minimal systemic absorption. The concerning Phase 3 observation was higher-than-expected rates of ulcer-related complications (osteomyelitis, cellulitis) in treated arms, interpreted in the context of a treatment that did not outperform vehicle.

Community-reported

Community use: essentially none documented. This is a discontinued investigational cream, not a self-use peptide.

Theoretical. none of practical relevance given topical-only exposure.

Interactions. none established.

Markers researchers commonly monitor

Not applicable as a self-use compound. In the trials, outcomes were clinical (wound/infection response, bacterial eradication) and local tolerability rather than blood markers, reflecting topical use with minimal systemic exposure.

Free for everyone. Safety information is never behind a paywall.

5Formulation and handling

Developed as a finished topical cream (Locilex 0.8%), not a peptide for . No calculator link applies.

6Commonly studied alongside

Standard diabetic-foot wound care, conventional topical and oral antibiotics (as comparators), other developmental antimicrobial peptides such as Omiganan and Melittin (research context).

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved; declined in 1999 and failed Phase 3 in 2016
European Union	Not authorised
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered
Sport	Not relevant; not listed by WADA

8Open questions

Why did a peptide with excellent in-vitro activity add nothing to good wound care — is the diabetic-foot ulcer model simply dominated by wound-care quality?
Can any topical antimicrobial peptide show benefit over vehicle in this setting?
Does the trial design (vehicle plus standardised wound care) make it almost impossible to show a drug effect?

9References

1Ge Y et al. (1999). In vitro antibacterial properties of pexiganan, an analog of magainin. Antimicrob Agents Chemother. PubMed · DOI
2Lipsky BA et al. (2008). Topical versus systemic antimicrobial therapy for treating mildly infected diabetic foot ulcers (pexiganan trials). Clin Infect Dis. PubMed
3Dipexium Pharmaceuticals (2016). OneStep-1 and OneStep-2 Phase 3 topline results announcement (press release / regulatory filing). PubMed
4Gottler LM, Ramamoorthy A (2009). Structure, membrane orientation, mechanism, and function of pexiganan. Biochim Biophys Acta. PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

10Community

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

30 Oct 2026Profile published — awaiting medical review

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