Peptidomimetics of efflux pump inhibitors potentiate the activity of levofloxacin in Pseudomonas aeruginosaThomas E Renau
Essential Therapeutics, Inc, 850Maude Avenue, Mountain View, CA 94043, USA
Bioorg Med Chem Lett 12:763-6. 2002
..A number of the new analogues were as active or more active than the lead, demonstrating that a peptide backbone is not essential for activity...
- It takes three to tango
Olga Lomovskaya
Nat Biotechnol 20:1210-2. 2002
Use of an efflux pump inhibitor to determine the prevalence of efflux pump-mediated fluoroquinolone resistance and multidrug resistance in Pseudomonas aeruginosaJane Kriengkauykiat
University of Southern California, School of Pharmacy, 1985 Zonal Ave, Los Angeles, CA 90089, USA
Antimicrob Agents Chemother 49:565-70. 2005
..aeruginosa. Our data support the fact that increased fluoroquinolone usage can negatively impact susceptibility of P. aeruginosa to multiple classes of antipseudomonal agents...
- Pharmacodynamics of levofloxacin against Pseudomonas aeruginosa with reduced susceptibility due to different efflux pumps: do elevated MICs always predict reduced in vivo efficacy?
David C Griffith
Mpex Pharmaceuticals, Inc 3030 Bunker Hill St, Suite 200, San Diego, CA 92109, USA
Antimicrob Agents Chemother 50:1628-32. 2006
..These data show that while the MexEF-OprN efflux pump can provide P. aeruginosa resistance to levofloxacin in vitro, it appears to be less efficient in providing resistance to levofloxacin in animal models of infection...
- Vacuuming the periplasm
Olga Lomovskaya
Mpex Pharmaceuticals, Inc, 5500 Campanile Dr, San Diego, CA 92182, USA
J Bacteriol 187:1879-83. 2005
- Waltzing transporters and 'the dance macabre' between humans and bacteria
Olga Lomovskaya
Mpex Pharmaceuticals, Inc 3030 Bunker Hill Street, Suite 200 San Diego, California 92109, USA
Nat Rev Drug Discov 6:56-65. 2007
..Here, we review recent advances in the field and describe various approaches used in combating efflux-mediated resistance...
- Quinazolinone fungal efflux pump inhibitors. Part 2: In vitro structure-activity relationships of (N-methyl-piperazinyl)-containing derivatives
William J Watkins
Essential Therapeutics, Inc, 850 Maude Ave, Mountain View, CA 94043, USA
Bioorg Med Chem Lett 14:5133-7. 2004
....
- Quinazolinone fungal efflux pump inhibitors. Part 3: (N-methyl)piperazine variants and pharmacokinetic optimization
William J Watkins
Essential Therapeutics, Inc, 850 Maude Ave, Mountain View, CA 94043, USA
Bioorg Med Chem Lett 17:2802-6. 2007
..albicans and C. glabrata over-expressing ABC-type efflux pumps are systematically explored. Rat protein binding and pharmacokinetics of selected analogues are reported...
Effect of oxygen limitation on the in vitro activity of levofloxacin and other antibiotics administered by the aerosol route against Pseudomonas aeruginosa from cystic fibrosis patientsPaula King
Mpex Pharmaceuticals, Inc, San Diego, CA 92121 1309, USA
Diagn Microbiol Infect Dis 66:181-6. 2010
..In contrast, levofloxacin maintains activity against P. aeruginosa under anaerobic or hypoxic conditions similar to those found in CF microaerophilic environments...
- In vitro pharmacodynamics of levofloxacin and other aerosolized antibiotics under multiple conditions relevant to chronic pulmonary infection in cystic fibrosis
Paula King
Mpex Pharmaceuticals, Inc, 11535 Sorrento Valley Road, San Diego, CA 92121 1309, USA
Antimicrob Agents Chemother 54:143-8. 2010
..The results of the study show that the high concentrations of levofloxacin readily achievable in the lung following aerosol delivery may be useful for the management of pulmonary infections in patients with cystic fibrosis...
- Levofloxacin reduces inflammatory cytokine levels in human bronchial epithelia cells: implications for aerosol MP-376 (levofloxacin solution for inhalation) treatment of chronic pulmonary infections
Ruslan Tsivkovskii
Mpex Pharmaceuticals, San Diego, CA, USA
FEMS Immunol Med Microbiol 61:141-6. 2011
....
- Conformationally-restricted analogues of efflux pump inhibitors that potentiate the activity of levofloxacin in Pseudomonas aeruginosa
Thomas E Renau
Essential Therapeutics, Inc, 850Maude Avenue, Mountain View, CA 94043, USA
Bioorg Med Chem Lett 13:2755-8. 2003
....
- Practical applications and feasibility of efflux pump inhibitors in the clinic--a vision for applied use
Olga Lomovskaya
Mpex Pharmaceuticals Inc, 3030 Bunker Hill Street, San Diego, CA 92109, USA
Biochem Pharmacol 71:910-8. 2006
..It is also apparent that some changes in regulatory decision-making regarding resistance would be very helpful in order to facilitate approval of agents aiming to reverse resistance and prevent its further development...
- Quinazolinone-based fungal efflux pump inhibitors. Part 1: Discovery of an (N-methylpiperazine)-containing derivative with activity in clinically relevant Candida spp
Rémy C Lemoine
Essential Therapeutics, Inc, 850 Maude Ave, Mountain View, CA 94043, USA
Bioorg Med Chem Lett 14:5127-31. 2004
..albicans is described. Attempts to improve the aqueous solubility of screening hits led to the discovery of an analog with greatly improved physical properties and activity against clinically-relevant Candida spp...
- On the mechanism of substrate specificity by resistance nodulation division (RND)-type multidrug resistance pumps: the large periplasmic loops of MexD from Pseudomonas aeruginosa are involved in substrate recognition
Weimin Mao
Essential Therapeutics Inc, 850 Maude Ave, Mountain View, CA 94043, USA
Mol Microbiol 46:889-901. 2002
..These results are consistent with the hypothesis that, in the case of RND transporters, the LPLs are directly implicated in substrate recognition and contain multiple sites of interaction for various structurally diverse compounds...
- MexXY-OprM efflux pump is necessary for a adaptive resistance of Pseudomonas aeruginosa to aminoglycosides
Didier Hocquet
, , , France
Antimicrob Agents Chemother 47:1371-5. 2003
..Altogether, these results indicate that the resistance process requires the rapid production of MexXY and the interaction of these proteins with the constitutively produced component OprM...
- Drug-induced conformational changes in multidrug efflux transporter AcrB from Haemophilus influenzae
Vishakha Dastidar
Department of Chemistry and Biochemistry, 620 Parrington Oval, Norman, OK 73019, USA
J Bacteriol 189:5550-8. 2007
..We report that the reactivity of specific cysteines with FM is affected by the presence of some but not all substrates. Our results suggest that substrates induce conformational changes in AcrB(HI)...
- Multidrug pump inhibitors uncover remarkable activity of plant antimicrobials
George Tegos
Department of Biology, Northeastern University, Boston, Massachusetts 02115, USA
Antimicrob Agents Chemother 46:3133-41. 2002
..These findings also suggest that plant antimicrobials might be developed into effective, broad-spectrum antibiotics in combination with inhibitors of MDRs...
