| Description |
Metallo-β-lactamase-IN-6 is a potent VIM-Type metallo-β-lactamase inhibitor with IC50s of 0.56 μM, 29.50 μM and 5.78 μM for VIM-2, VIM-1 and VIM-5. Metallo-β-lactamase-IN-6 displays potent synergistic antibacterial activity with Meropenem against engineered Escherichia coli strains and intractable clinically isolated Pseudomonas aeruginosa producing VIM-2 MBL[1].
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| Related Catalog |
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| Target |
IC50: 0.56 μM (VIM-2), 29.50 μM (VIM-1), 5.78 μM (VIM-5)[1]
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| In Vitro |
Metallo-β-lactamase-IN-6 (compound 55) (10 μM; 18 - 20 hours) can potentiate Meropenem activity against VIM-2 mediated antibacterial resistance with FIC index values of 0.05[1]. Metallo-β-lactamase-IN-6 (1, 10, 100 μM; 18 - 20 hours) can penetrate E. coli outer membrane and restore Meropenem activity against PBP3 by blocking destructive effect of VIM-2 enzyme to Meropenem[1]. Metallo-β-lactamase-IN-6 (100 μM) potentiates the antibacterial activity of Meropenem against PA W35 with FIC index values of 0.25[1].
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| In Vivo |
Metallo-β-lactamase-IN-6 (100 mg/kg; IP; single) reaches plasma concentration peak about 9 min after injection with an effective maximum concentration of 142.8 μg/ml, and the T1/2 is 1.24 hours[1]. Metallo-β-lactamase-IN-6 (500, 1000, or 2000 mg/kg; IP; single, observe for 14 days) does not result in any significant toxic effects and is well-tolerated by mice at a dose of ≤ 2000 mg/kg[1]. Pharmacokinetic Parameters of Metallo-β-lactamase-IN-6 in male female ICR mice[1]. IP (100 mg/kg) T1/2 (h) 1.243 Cmax (μg/mL) 142.8 Tmax (h) 0.151 Vd (mL/kg) 535.804 CL (mL/h/kg) 248.512 AUC0-∞ (μg/mL·h) 896 Animal Model: Female ICR mice (180-220 g)[1] Dosage: 100 mg/kg Administration: IP; single (Pharmacokinetics Analysis) Result: Plasma concentration reached its peak about 9 min after injection with an effective maximum concentration of 142.8 μg/ml, and the T1/2 was 1.24 hours. Animal Model: Female ICR mice (n=5)[1] Dosage: 500, 1000, or 2000 mg/kg Administration: IP; single, observed for 14 days Result: Did not result in any significant toxic effects and was well-tolerated by mice at a dose of ≤ 2000 mg/kg.
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| References |
[1]. Yan YH, Li W, Chen W, et al. Structure-guided optimization of 1H-imidazole-2-carboxylic acid derivatives affording potent VIM-Type metallo-β-lactamase inhibitors. Eur J Med Chem. 2022;228:113965.
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