GSK2556286 Is a Novel Antitubercular Drug Candidate Effective with the Potential To Shorten Tuberculosis Treatment.

Journal:
Antimicrobial agents and chemotherapy, Volume: 66, Issue: 6
Published:
June 21, 2022
PMID:
35607978
Authors:
Eric L Nuermberger EL, Maria Santos Martínez-Martínez MS, Olalla Sanz O, Beatriz Urones B, Jorge Esquivias J, Heena Soni H, Rokeya Tasneen R, Sandeep Tyagi S, Si-Yang Li SY, Paul J Converse PJ, Helena I Boshoff HI, Gregory T Robertson GT, Gurdyal S Besra GS, Katherine A Abrahams KA, Anna M Upton AM, Khisimuzi Mdluli K, Gary W Boyle GW, Sam Turner S, Nader Fotouhi N, Nicholas C Cammack NC, Juan Miguel Siles JM, Marta Alonso M, Jaime Escribano J, Joel Lelievre J, Joaquin Rullas-Trincado J, Esther Pérez-Herrán E, Robert H Bates RH, Gareth Maher-Edwards G, David Barros D, Lluís Ballell L, Elena Jiménez E
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 [IC] = 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).