BB-3497

BB-3497 is a potent, orally active and selective peptide deformylase (PDF) inhibitor. BB-3497 is highly selective for PDF (IC₅₀ = 7 nM for E. coli PDF.Ni) over the other mammalian metalloenzymes (MMP-1/2/3/7 and enkephalinase). BB-3497 exhibits potent activity against gram-positive bacteria and some gram-negative pathogens. BB-3497 protects mice from infection in systemic models of Staphylococeus aureus. BB-3497 can be used for anti-bacterial infection research^[1]. In Vitro:BB-3497 binds to PDF such that the oxygen atoms of its N-formyl-hydroxylamine group occupy the positions of the two Ni-bound water molecules observed in the PDF-Met-Ala-Ser product complex^[1].
BB-3497 shows superior in vitro antibacterial activity against E. coli DH5α and E. coli BL21(DE3) strains harboring a control plasmid (pET24) or pET24-PDF, with MIC values of 4, 8, 32, and 128 μg/mL, but shows an MIC of >128 μg/mL against an E. coli formyltransferase mutant, confirming that its antibacterial action is mediated through PDF inhibition^[1].
BB-3497 (4-8x MIC, 24 h) results in <1-log-unit decreases in viable counts of S. aureus and E. coli, conforming its antibacterial effect^[1].
BB-3497 (2-4x MIC, 24 h) results in resistant mutants at frequencies of 1 x 10^-7 for E. coli and 2 x 10^-7 for S. aureus, with high-level resistance conferred by mutations in the fmt gene and low-level resistance exhibited by mutants having a wild-type def-fmt operon^[1]. In Vivo:BB-3497 (3-100 mg/kg, p.o. or i.v., single dose at 1 h after bacterial challenge) protects mice from infection with S. aureus and methicillin-resistant S. aureus^[1].