2. Academic Validation
  3. GSK2556286 Is a Novel Antitubercular Drug Candidate Effective In Vivo with the Potential To Shorten Tuberculosis Treatment

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

  • Antimicrob Agents Chemother. 2022 Jun 21;66(6):e0013222. doi: 10.1128/aac.00132-22.
Eric L Nuermberger 1,  Maria Santos Martínez-Martínez 2,  Olalla Sanz 2,  Beatriz Urones 2,  Jorge Esquivias 2,  Heena Soni 1,  Rokeya Tasneen 1,  Sandeep Tyagi 1,  Si-Yang Li 1,  Paul J Converse 1,  Helena I Boshoff 3,  Gregory T Robertson 4,  Gurdyal S Besra 5,  Katherine A Abrahams 5,  Anna M Upton 6,  Khisimuzi Mdluli 6,  Gary W Boyle 7,  Sam Turner 7,  Nader Fotouhi 6,  Nicholas C Cammack 2,  Juan Miguel Siles 2,  Marta Alonso 2,  Jaime Escribano 2,  Joel Lelievre 2,  Joaquin Rullas-Trincado 2,  Esther Pérez-Herrán 2,  Robert H Bates 2,  Gareth Maher-Edwards 8,  David Barros 2,  Lluís Ballell 2,  Elena Jiménez 2
Affiliations

Affiliations

  • 1 Center for Tuberculosis Research, Division of Infectious Diseases, Johns Hopkins Universitygrid.21107.35grid.471401.7grid.21107.35 School of Medicine, Baltimore, Maryland, USA.
  • 2 Diseases of the Developing World, GlaxoSmithKline R+D Limited, Tres Cantos, Madrid, Spain.
  • 3 Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • 4 Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA.
  • 5 Institute of Microbiology and Infection, School of Biosciences, University of Birminghamgrid.6572.6, Birmingham, United Kingdom.
  • 6 TB Alliance: Global Alliance for Tuberculosis Drug Development, New York, New York, USA.
  • 7 GSK: Research, GlaxoSmithKline R&D, Ware, United Kingdom.
  • 8 GSK, Brentford, Middlesex, United Kingdom.
PMID: 35607978 DOI: 10.1128/aac.00132-22
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).

Keywords

GSK2556286; Mycobacterium tuberculosis; mouse; pharmacology; relapse; tuberculosis.

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