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Infectious disease

Tuberculosis (TB)

Mycobacterium tuberculosis cytochrome bc1

Cell culture and mouse studies identified an inhibitor of M. tuberculosis cytochrome bc1 that could be useful for treating multidrug-resistant (MDR) TB. A screen for inhibitors of M. tuberculosis growth in infected murine macrophages identified a class of imidazopyridine amides that prevented bacterial replication with low nanomolar potency and were not cytotoxic to host cells. The best compound, Q203, inhibited bacterial respiration in vitro and decreased bacterial load and lung pathology compared with vehicle in MDR M. tuberculosis-infected mice. In vitro and in mice, Q203 had comparable activity to Sirturo bedaquiline, which is marketed by Johnson & Johnson to treat MDR pulmonary TB. Next steps could include studies in additional preclinical models of TB infection (see Found in translation: Institute Pasteur Korea, page 4).

SciBX 6(32); doi:10.1038/scibx.2013.865
Published online Aug. 22, 2013

Patent pending; licensed to Qurient Co. Ltd.

Pethe, K. et al. Nat. Med.; published online Aug. 4, 2013;
Contact: Kevin Pethe, Institute Pasteur Korea, Seongnam-si, South Korea