| Literature DB >> 35607978 |
Eric L Nuermberger1, Maria Santos Martínez-Martínez2, Olalla Sanz2, Beatriz Urones2, Jorge Esquivias2, Heena Soni1, Rokeya Tasneen1, Sandeep Tyagi1, Si-Yang Li1, Paul J Converse1, Helena I Boshoff3, Gregory T Robertson4, Gurdyal S Besra5, Katherine A Abrahams5, Anna M Upton6, Khisimuzi Mdluli6, Gary W Boyle7, Sam Turner7, Nader Fotouhi6, Nicholas C Cammack2, Juan Miguel Siles2, Marta Alonso2, Jaime Escribano2, Joel Lelievre2, Joaquin Rullas-Trincado2, Esther Pérez-Herrán2, Robert H Bates2, Gareth Maher-Edwards8, David Barros2, Lluís Ballell2, Elena Jiménez2.
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).Entities:
Keywords: GSK2556286; Mycobacterium tuberculosis; mouse; pharmacology; relapse; tuberculosis
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Year: 2022 PMID： 35607978 PMCID： PMC9211396 DOI： 10.1128/aac.00132-22
Source DB: PubMed Journal: Antimicrob Agents Chemother ISSN： 0066-4804 Impact factor: 5.938