Therapeutic potential of peptide deformylase inhibitors.
Peptide deformylase (PDF) is an attractive target for antibacterial drug discovery. Progress in the biological characterisation of the enzyme, coupled with newly obtained mechanistic and structural insight, enabled the pharmaceutical industry to discover potent PDF inhibitors that can be considered as clinical development candidates for this new class of antibacterial agents. The in vitro and in vivo data for several lead PDF inhibitors suggest that the current PDF inhibitors are most suitable for the treatment of respiratory tract infections and they are not cross-resistant to the current clinically used antibiotics. Two PDF inhibitors, BB-83698 and VIC-104959, have progressed to Phase I clinical trials by intravenous and oral administration, respectively. Both of these compounds show promising in vitro and in vivo efficacy and an excellent safety profile. The pharmacokinetics in humans for both of the compounds suggest the possibility of a twice-daily dosing regimen for clinical use. Thus far, all of the data suggest a promising future for this new class of antibacterial agents.
Chen
D
D
Vicuron Pharmaceuticals, 34790 Ardentech Court, Fremont, CA 94555, USA.
Yuan
Z
Z
D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D008826:Microbial Sensitivity Tests
D000900:Anti-Bacterial Agents; C481664:BB-83698; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D000581:Amidohydrolases; C084507:peptide deformylase