The aim of this work is develop a novel protein synthesis inhibitor for the treatment of TB. The starting point of the collaboration with Anacor Pharmaceuticals were inhibitors that demonstrated proof of concept on-target activity and good in vitro activity against M. tuberculosis. We have found that modifications to the structure of a Gram-negative LeuRS inhibitor, which is efficacious in humans, give rise to more potent inhibitors that are preferentially active on M. tuberculosis. Work on several advanced leads demonstrate excellent in vivo activity in both acute and chronic mouse TB models at ≤10 mg/kg/d (all animal studies were ethically reviewed and carried out in accordance with European Directive 2010/63/EU and the GSK Policy on the Care, Welfare and Treatment of Animals). Work is on-going to progress these further.