| Description |
PF-5081090 (LpxC-4) is a potent LpxC inhibitor, is a rapidly bactericidal with broad-spectrum activity. PF-5081090 serves as a regulator of lipid A biosynthesis in Gram-negative pathogens[1][2].
|
| Related Catalog |
|
| In Vitro |
PF-5081090 shows strong potency against a broad spectrum of Gram-negative pathogens with IC50s of 1.1 nM (P. aeruginosa), 0.069 nM (K. pneumonia) and MIC90s of 1 μg/mL (P. aeruginosa, K. pneumoniae), 0.25 μg/mL (E. coli), 0.5 μg/mL (Enterobacter spp), 2 μg/mL (S. maltophilia)[1]. PF-5081090 (0.25 μg/mL; 0-50 h) demonstrates sustained bactericidal activities against P. aeruginosa UC12120 (A), PA-1955 (B), and K. pneumoniae KP-1487[1]. PF-5081090 (32 mg/L) increases antibiotic susceptibility in Acinetobacter baumannii with rifampicin, vancomycin, azithromycin, imipenem and amikacin[2]. PF-5081090 (32 mg/L) inhibits lipid A biosynthesis, and significantly increases cell permeability in A. baumannii[2].
|
| In Vivo |
PF-5081090 (8.75, 75, 300 mg/kg; s.c.; single dose) exhibits a exposure increasing in linear manner across the dose range in mice, with area under the concentration-time curve (AUC) and maximum concentration of drug in serum (Cmax) increasing with a proportional increase in dose[1]. PF-5081090 shows potent efficacies against sentinel strains of P. aeruginosa and K. pneumonia in CD-1 mice, with effective dose (ED50) ranging from 7.4-55.9 mg/kg (against acute septicemia model), <25 mg/kg (against pneumonia model), and 16.8 mg/kg (against neutropenic thigh model) in mice infected with P. aeruginosa PA-1950[1]. Pharmacokinetics of PF-5081090 in CD-1 micea[1] Dose (mg/kg) Cmax (mg/L) Tmax (h) AUC (h•mg/L) Free AUC (h•mg/L) T1/2 (h) CL (L/h/kg) Vss (L/kg) 18.75 5.02 0.25 5.09 1.58 0.6 3.79 2.20 75 15.50 0.33 17.60 5.46 0.69 4.32 3.30 300 75.40 0.33 76.30 23.70 0.68 3.92 2.53a Following single subcutaneous doses.
|
| References |
[1]. Tomaras AP, et al. LpxC inhibitors as new antibacterial agents and tools for studying regulation of lipid A biosynthesis in Gram-negative pathogens. mBio. 2014 Sep 30;5(5):e01551-14. [2]. García-Quintanilla M, et al. Inhibition of LpxC Increases Antibiotic Susceptibility in Acinetobacter baumannii. Antimicrob Agents Chemother. 2016 Jul 22;60(8):5076-9.
|
