KKL-10

Description: KL-10 is a small-molecule ribosome rescue inhibitor that possesses a broad-spectrum of antimicrobial activity against bacteria. KKL-10 exhibited exceptional antimicrobial activity against both attenuated and fully virulent strains of F. tularensis in vitro and during ex vivo infection. Addition of KKL-10 to macrophages or liver cells at any time after infection by F. tularensis prevented further bacterial proliferation. When macrophages were stimulated with the proinflammatory cytokine gamma interferon before being infected by F. tularensis, addition of KKL-10 reduced intracellular bacteria by > 99%, indicating that the combination of cytokine-induced stress and a nonfunctional ribosome rescue pathway is fatal to F. tularensis. KKL-10 was not cytotoxic to eukaryotic cells in culture. Therefore, KKL-10 is a good lead compound for antibiotic development.

References: Antimicrob Agents Chemother. 2016 May 23; 60(6):3276-82.