A40926

A40926 is a glycopeptide antibiotic that targets the bacterial cell wall peptidoglycan precursor D-alanyl-D-alanine (D-Ala-D-Ala). A40926 irreversibly inhibits cell wall synthesis by competitively binding to this target, and has high bactericidal activity against Gram-positive bacteria (such as Staphylococcus, Streptococcus) and Neisseria gonorrhoeae, with MIC=0.06-2 μg/mL, and is also effective against penicillin-resistant strains. A40926 blocks peptidoglycan cross-linking, destroys cell wall integrity, and causes bacterial lysis and death. A40926 has a fat-soluble fatty acid structure, which can increase serum concentrations and prolong the duration of action (e.g., the terminal half-life in rats is 61.22 h)^[1][2]. In Vitro:A40926 shows strong inhibitory activity against Gram-positive bacteria (such as Staphylococcus aureus and Streptococcus) and Neisseria gonorrhoeae, with MIC=0.004-32 μg/mL. The median MIC against clinical isolates of Neisseria gonorrhoeae is 1 μg/mL, which is significantly lower than Teicoplanin (HY-A0097) and Vancomycin (HY-B0671)^[1].
A40926 (4-16 μg/mL; 5 h) could kill 99.9%-99.99% of clinical isolates within 5 h at concentrations 4 to 8 times the MIC, including penicillin-resistant and spectinomycin (HY-B1828)-resistant strains, showing rapid bactericidal activity^[1]. In Vivo:A40926 (10 mg/kg; sc; single dose) improves the sepsis model of CD-1 mice and reduces the infection of mice with Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae. The effect is slightly lower than that of Teicoplanin (HY-A0097) (ED₅₀ is 1.9, 0.33, and 0.38 mg/kg, respectively), but the concentration in serum is significantly higher and lasts longer than Teicoplanin^[1].
In the pharmacokinetic model of male CD rats, A40926 (10 mg/kg; iv/sc; single dose) shows decayed plasma concentration in a power function after intravenous injection, with a terminal half-life of 61.22 h, a subcutaneous bioavailability of nearly 90%, and a urinary excretion rate of 35.9% at 120 h^[2].