PF-04753299 is an inhibitor of LpxC (IC₅₀= 1.37 nM), a bacterial deacetylase involved in the biosynthesis of LPS lipid A.¹It is selective for LpxC over a panel of 16 human matrix metalloproteinases (MMPs; K_is = >1 µM for all). PF-04753299 is active againstP. aeruginosa, K. pneumoniae, E. coli, E. aerogenes, C. freundii, andA. baumannii(MIC₉₀s = 4, 16, 2, 4, 8, and 32 µg/ml, respectively).In vivo, PF-04753299 reduces splenic bacterial burden in a mouse model of systemicP. aeruginosainfection (ED₅₀= 35 mg/kg).

1.Brown, M.F., Reilly, U., Abramite, J.A., et al.Potent inhibitors of LpxC for the treatment of Gram-negative infectionsJ. Med. Chem.55(2)914-923(2012)