Pexiganan (MSI-78) is a 22-amino-acid synthetic analog of magainin 2, an antimicrobial peptide originally isolated from the skin of the African clawed frog (Xenopus laevis). It has broad-spectrum bactericidal activity and was developed as a topical cream (Locilex) for infected diabetic foot ulcers. Despite reaching Phase III clinical trials, pexiganan was not approved by the FDA, which determined it was not superior to existing treatments.
Category: Antimicrobial / Immune. Evidence rating: C (early/mixed human evidence).
Clinical status: Phase III completed. Two NDA submissions to FDA (1999 and 2016) — both unsuccessful. Not approved in any jurisdiction.
Pexiganan is a cationic alpha-helical antimicrobial peptide that kills bacteria through membrane disruption. It binds to anionic bacterial membrane phospholipids via electrostatic interactions, inserts into the lipid bilayer, and forms toroidal pores that cause rapid membrane permeabilization and…
Safety considerations: Topical formulation showed good local tolerability in clinical trials; Application site reactions (erythema, pruritus) reported in Phase III studies; Systemic absorption from topical application is minimal.
Reviewed by the PeptideAtlas Editorial Team.
| Molecular weight | ~2477 g/mol |
|---|---|
| CAS number | 172820-23-4 |
| Production method | synthetic |
| Anti-doping status | not-listed |
| US regulatory status | Not FDA-approved. Two NDA submissions (1999, 2016) were unsuccessful. Development discontinued. |
Related peptides: LL-37, Beta-Defensins, Alpha-Defensins.
The FDA rejected pexiganan twice. In 1999, the agency determined the drug did not demonstrate adequate efficacy compared to the oral antibiotic comparator. In 2016, new Phase III trials failed to show superiority over vehicle cream alone. The bar for topical antimicrobial approval proved difficult to meet.
Pexiganan is a synthetic analog of magainin 2, a 23-amino-acid antimicrobial peptide discovered by Dr. Michael Zasloff in 1987 in the skin of the African clawed frog (Xenopus laevis). Pexiganan was optimized for improved antimicrobial potency.
Yes, in vitro. Pexiganan shows activity against MRSA, VRE, and multi-drug-resistant Gram-negative bacteria because its mechanism (membrane disruption) is fundamentally different from conventional antibiotics. However, this in vitro activity did not translate to an approved clinical application.