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Antimicrob Agents Chemother ; 66(6): e0013222, 2022 06 21.
Article in English | MEDLINE | ID: mdl-35607978

ABSTRACT

As a result of a high-throughput compound screening campaign using Mycobacterium tuberculosis-infected macrophages, a new drug candidate for the treatment of tuberculosis has been identified. GSK2556286 inhibits growth within human macrophages (50% inhibitory concentration [IC50] = 0.07 µM), is active against extracellular bacteria in cholesterol-containing culture medium, and exhibits no cross-resistance with known antitubercular drugs. In addition, it has shown efficacy in different mouse models of tuberculosis (TB) and has an adequate safety profile in two preclinical species. These features indicate a compound with a novel mode of action, although still not fully defined, that is effective against both multidrug-resistant (MDR) or extensively drug-resistant (XDR) and drug-sensitive (DS) M. tuberculosis with the potential to shorten the duration of treatment in novel combination drug regimens. (This study has been registered at ClinicalTrials.gov under identifier NCT04472897).


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Tuberculosis , Animals , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Macrophages , Mice , Microbial Sensitivity Tests , Tuberculosis/drug therapy , Tuberculosis, Multidrug-Resistant/drug therapy
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