[1] It is a synthetic cyclic beta hairpin peptidomimetic based on the cationic antimicrobial peptide protegrin I (PG-1) and the first example of an outer membrane protein-targeting antibiotic class with a novel, nonlytic mechanism of action, highly active and selective against the protein transporter LptD of Pseudomonas aeruginosa.

[2] In preclinical studies the compound was highly active on a broad panel of clinical isolates including multi-drug resistant Pseudomonas bacteria with outstanding in vivo efficacy in sepsis, lung, and thigh infection models.

[4][5] Iterative rounds of synthesis generated analogues with an increasingly potent and selective profile producing nanomolar range compounds specifically against Pseudomonas spp.

[8] Final optimization led to the discovery of murepavadin,[1][2] with remarkable Pseudomonas-specific activity in vitro and in vivo that has high plasma stability across species and is non-hemolytic at 100 μg/mL.

In phase I clinical trial in healthy volunteers, single doses were well tolerated at plasma concentrations expected to meet or exceed efficacious levels, with no serious adverse events reported.