TY - JOUR
T1 - GSK2556286 Is a Novel Antitubercular Drug Candidate Effective In Vivo with the Potential To Shorten Tuberculosis Treatment
AU - Nuermberger, Eric L.
AU - Martínez-Martínez, Maria Santos
AU - Sanz, Olalla
AU - Urones, Beatriz
AU - Esquivias, Jorge
AU - Soni, Heena
AU - Tasneen, Rokeya
AU - Tyagi, Sandeep
AU - Li, Si Yang
AU - Converse, Paul J.
AU - Boshoff, Helena I.
AU - Robertson, Gregory T.
AU - Besra, Gurdyal S.
AU - Abrahams, Katherine A.
AU - Upton, Anna M.
AU - Mdluli, Khisimuzi
AU - Boyle, Gary W.
AU - Turner, Sam
AU - Fotouhi, Nader
AU - Cammack, Nicholas C.
AU - Siles, Juan Miguel
AU - Alonso, Marta
AU - Escribano, Jaime
AU - Lelievre, Joel
AU - Rullas-Trincado, Joaquin
AU - Pérez-Herrán, Esther
AU - Bates, Robert H.
AU - Maher-Edwards, Gareth
AU - Barros, David
AU - Ballell, Lluís
AU - Jiménez, Elena
N1 - Publisher Copyright:
Copyright © 2022 American Society for Microbiology. All Rights Reserved.
PY - 2022/6
Y1 - 2022/6
N2 - 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 mM), 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).
AB - 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 mM), 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).
KW - KEYWORDS GSK2556286
KW - Mycobacterium tuberculosis
KW - mouse
KW - pharmacology
KW - relapse
KW - tuberculosis
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U2 - 10.1128/aac.00132-22
DO - 10.1128/aac.00132-22
M3 - Article
C2 - 35607978
AN - SCOPUS:85132454109
SN - 0066-4804
VL - 66
JO - Antimicrobial agents and chemotherapy
JF - Antimicrobial agents and chemotherapy
IS - 6
ER -