RESUMEN
This study evaluated the in vitro activity of KHP-3757 (a novel LpxC inhibitor) and comparator agents against recent, geographically diverse, Pseudomonas aeruginosa isolates from a global surveillance program as well as molecularly characterized extended-spectrum-ß-lactamase-positive, metallo-ß-lactamase-positive, and colistin-resistant strains. KHP-3757 (MIC50/90, 0.25/0.5â¯mg/L; 97.4% inhibited at ≤0.5â¯mg/L) demonstrated potent in vitro activity based on MIC90 values against P. aeruginosa isolates including extended-spectrum-ß-lactamase-positive, metallo-ß-lactamase-positive, and colistin-resistant strains outperforming other comparator agents.
Asunto(s)
Amidohidrolasas/antagonistas & inhibidores , Antibacterianos/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Colistina/farmacología , Farmacorresistencia Bacteriana/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/enzimología , Pseudomonas aeruginosa/aislamiento & purificación , beta-Lactamasas/metabolismoRESUMEN
By applying conformational restrictions, we were able to discover highly potent 1,3-diaminopyrimidine based covalent inhibitors of BTK, such as 8a (IC50=3.76 nM), and providing useful information of its active conformation. We are developing these novel small molecule covalent inhibitors of BTK toward oral agents for Rheumatoid arthritis.