Abstract

As a result of a high-throughput compound screening campaign of Mycobacterium tuberculosis infected macrophages, a new preclinical drug candidate for the treatment of tuberculosis has been identified. GSK2556286 inhibits growth within human macrophages (IC50 = 0.07 μM), is active against extracellular bacteria in cholesterol-containing culture media 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 or extensively-resistant (M/XDR) and drug-sensitive (DS) M. tuberculosis with the potential to shorten the duration of treatment in novel combination drug regimens.

Details

Title
GSK2556286 is a novel antitubercular drug candidate effective in vivo with the potential to shorten tuberculosis treatment
Author
Nuermberger, Eric; Maria Santos Martínez; Sanz, Olalla; Urones, Beatriz; Esquivias, Jorge; Soni, Heena; Tasneen, Rokeya; Tyagi, Sandeep; Si-Yang, Li; Converse, Paul J; Boshoff, Helena I; Robertson, Gregory Thomas; Besra, Gurdyl; Abrahams, Katherine A; Upton, Anna; Mdluli, Khisimuzi; Boyle, Gary W; Turner, Sam; Fotouhi, Nader; Cammack, Nicholas C; Juan Miguel Siles; Alonso, Marta; Excribano, Jaime; Lelièvre, Joël; Perez-Herran, Esther Maria; Bates, Robert H; Maher-Edwards, Gareth X; Barros-Aguirre, David; Ballell, Lluís; Jimenez, Elena N
University/institution
Cold Spring Harbor Laboratory Press
Section
New Results
Publication year
2022
Publication date
Feb 6, 2022
Publisher
Cold Spring Harbor Laboratory Press
ISSN
2692-8205
Source type
Working Paper
Language of publication
English
ProQuest document ID
2625926660
Copyright
© 2022. This article is published under http://creativecommons.org/licenses/by-nd/4.0/ (“the License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.