Gepotidacin is a novel triazaacenaphthylene inhibitor of bacterial type II topoisomerase.

Gepotidacin has in vitro activity against causative pathogens of acute bacterial skin and skin structure infections (ABSSSIs) [3]. Gepotidacin that inhibits bacterial DNA gyrase and topoisomerase IV via a unique mechanism and has demonstrated in vitro activity against gram-negative and gram-positive bacterias, including drug-resistant strains, and also targets pathogens associated with other conventional and biothreat infections. The MIC50 and MIC90 for gepotidacin against the 25 N. Gonorrhoeae isolate tested are 0.12 and 0.25 μg/mL, respectively [1]. The gepotidacin MIC90s are as follows: Streptococcus pyogenes (0.25 μg/mL); Escherichia coli (2 μg/mL); Moraxella catarrhalis (≤0.06 μg/mL); Streptococcus pneumoniae (0.25 μg/mL); Haemophilus influenzae (1 μg/mL); Clostridium perfringens (0.5 μg/mL); and Shigella spp. (1 μg/mL) [2].

ELF penetration ratios vary between 1.1 and 1.4. GSK2140944 exhibits minimum inhibitory concentrations (MICs) of 0.125 to 0.5 mg/L against six MRSA isolates. The average area under the curve (AUC)/MIC ratios necessary for bacterial stasis and a decrease of 1 log-unit are 59.3 ± 34.6 and 148.4 ± 83.3, respectively. The maximal reductions observed amount to 1.1 to 3.1 log10 CFU in neutropenic mice [4].