GSK2556286 is a novel antitubercular drug candidate effective in vivo with the potential to shorten tuberculosis treatment

• DOI: 10.1101/2022.02.04.479214
• Publication Date: 2022-02-06T17:45:18Z
• Authors: Eric L. Nuermberger; Maria Santos Mart...; Olalla Sanz; Beatriz Urones; Jorge Esquivias; Heena Soni; Rokeya Tasneen; Sandeep Tyagi; Si-Yang Li; Paul J. Converse; Helena I. Boshoff; Gregory T Robertson; Gurdyal S Besra; Katherine A. Abra...; Anna M Upton; Khisimuzi Mdluli; Gary W Boyle; Sam Turner; Nader Fotouhi; Nicholas C. Cammack; Juan Miguel Siles; Marta Alonso; Jaime Escribano; Joel Lelievre; Esther Pérez-Herrán; Robert H. Bates; Gareth Maher-Ewards; David Barros; Lluís Ballell; Elena Jiménez
• Keywords: Mode of Action

Abstract As a result of high-throughput compound screening campaign Mycobacterium tuberculosis infected macrophages, new preclinical drug candidate for the treatment has been identified. GSK2556286 inhibits growth within human macrophages (IC 50 = 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 shown efficacy different mouse models (TB) an adequate safety profile two species. These features indicate novel mode action, although still not fully defined, that effective both multidrug or extensively-resistant (M/XDR) drug-sensitive (DS) M. potential to shorten duration combination regimens. One Sentence Summary action potentially able contribute shortening TB chemotherapy.