| Literature DB >> 31451507 |
Kevin M Krause1, Cat M Haglund2, Christy Hebner2, Alisa W Serio2, Grace Lee2, Vincent Nieto2, Frederick Cohen2, Timothy R Kane2, Timothy D Machajewski2, Darrin Hildebrandt2, Chris Pillar3, Mary Thwaites3, Danielle Hall3, Lynn Miesel4, Meredith Hackel5, Amanda Burek2, Logan D Andrews2, Eliana Armstrong2, Lee Swem2, Adrian Jubb2, Ryan T Cirz2.
Abstract
New drugs with novel mechanisms of resistance are desperately needed to address both community and nosocomial infections due to Gram-negative bacteria. One such potential target is LpxC, an essential enzyme that catalyzes the first committed step of lipid A biosynthesis. Achaogen conducted an extensive research campaign to discover novel LpxC inhibitors with activity against Pseudomonas aeruginosa We report here the in vitro antibacterial activity and pharmacodynamics of ACHN-975, the only molecule from these efforts and the first ever LpxC inhibitor to be evaluated in phase 1 clinical trials. In addition, we describe the profiles of three additional LpxC inhibitors that were identified as potential lead molecules. These efforts did not produce an additional development candidate with a sufficiently large therapeutic window and the program was subsequently terminated.Entities:
Keywords: LpxC; Pseudomonas aeruginosazzm321990
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Year: 2019 PMID： 31451507 PMCID： PMC6811409 DOI： 10.1128/AAC.00977-19
Source DB: PubMed Journal: Antimicrob Agents Chemother ISSN： 0066-4804 Impact factor: 5.191