Metallo-β-lactamase-IN-6 is a highly effective inhibitor of VIM-Type metallo-β-lactamase, demonstrating IC50 values of 0.56 μM, 29.50 μM, and 5.78 μM for VIM-2, VIM-1, and VIM-5, respectively. Additionally, Metallo-β-lactamase-IN-6 exhibits potent synergistic antibacterial properties when combined with Meropenem, particularly against engineered Escherichia coli strains and clinically isolated Pseudomonas aeruginosa carrying the VIM-2 MBL gene [1].

Metallo-β-lactamase-IN-6 (compound 55) (10 μM; 18-20 hours) enhances Meropenem's efficacy against VIM-2 mediated antibacterial resistance, evidenced by FIC index values of 0.05 [1]. At concentrations of 1, 10, and 100 μM over 18-20 hours, it breaches the E. coli outer membrane, revitalizing Meropenem's action against PBP3 by neutralizing the VIM-2 enzyme's adverse impact [1]. Furthermore, at 100 μM, it boosts Meropenem's antibacterial potency against PA W35, indicated by FIC index values of 0.25 [1].

Administered intraperitoneally at a single dose of 100 mg/kg, Metallo-β-lactamase-IN-6 reaches a peak plasma concentration of approximately 142.8 μg/mL around 9 minutes post-injection, with a half-life of 1.24 hours, indicating swift systemic availability and moderate persistence in the body [1]. When administered as a single intraperitoneal dose of 500, 1000, or 2000 mg/kg, Metallo-β-lactamase-IN-6 displayed no significant toxic effects and was well-tolerated in female ICR mice up to the highest tested dose of 2000 mg/kg over a 14-day observation period. These findings suggest that Metallo-β-lactamase-IN-6 is quickly absorbed and metabolized, with a favorable safety profile in the tested mouse model [1].