phenylalanine-arginine β-naphthylamide

Phenylalanine-arginine β-naphthylamide (PAβN, also known as MC-207,110) is a peptidomimetic small molecule that acts as a broad-spectrum bacterial efflux pump inhibitor (EPI). Discovered in 1999 through a collaboration between Microcide Pharmaceuticals and Daiichi Pharmaceutical, PAβN was identified as a potentiator of fluoroquinolone antibiotics (such as levofloxacin) against multidrug-resistant Gram-negative bacteria, particularly *Pseudomonas aeruginosa*. It acts as a competitive substrate for Resistance-Nodulation-Division (RND) family efflux pumps, including MexAB-OprM, MexCD-OprJ, and MexEF-OprN in *P. aeruginosa*, as well as AcrAB-TolC in *Escherichia coli*. By competing with antibiotics for efflux, PAβN increases their intracellular concentration and restores susceptibility. Additionally, at higher concentrations, PAβN has been shown to permeabilize the bacterial outer membrane. Although widely used as a reference research tool, its development as a therapeutic was limited by mammalian toxicity, including nephrotoxicity and neuromuscular blockade.

Other names

PAbetaNPAbNPAβNPhe-Arg β-naphthylamidePhe-Arg-β-naphthylamidephenylalanyl arginyl β-naphthylamidephenylalanyl-arginyl-β-naphthylamide