title: MC-207110 Daiichi Seiyaku/Microcide Pharmaceuticals.
abstract: Microcide and Daiichi are collaborating on the discovery of new bacterial efflux pump inhibitorsfor the treatment of drug-resistant Pseudomonas aeruginosa and other bacterial infections. The bacterial efflux pump technology program focuses on Gram-negative bacteria that have developed antibiotic resistance by means of the efflux pump [192681], [341408]. MC-207110 was the initial screening hitfrom Microcide's library and is a low molecular weight dipeptide amide, which shows minimal antibacterial activity but potentiated the activity of levofloxacin by 8-fold at 10 microg/ml. This lead is being optimized to improve on its biological and pharmacological profile [341183]. Optimization studies have been conducted on MC-207110, yielding a class of broad-spectrum efflux pump inhibitors for P aeruginosa. A member of this class has demonstrated in vivo activity against P aeruginosa in a murine neutropenic thigh model [351686].
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Department of Infectious Diseases--Microbiology, Wallingford, CT 06492, USA. John.Barrett@bms.com
authors.forename: J F
authors.initials: JF
authors.lastname: Barrett
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000378:metabolism; D004151:Dipeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D004357:Drug Synergism; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D004151:Dipeptides; C419365:phenylalanine arginine beta-naphthylamide