Developing leads to shorten duration of TB chemotherapy: SHORTEN-TB

Overview

Developing Lead Compounds to Shorten the duration of Tuberculosis Chemotherapy (SHORTEN-TB) is an effort to build upon lessons learned from the previous HIT-TB program and other recent advances in understanding how rate-determining steps that direct drug concentrations in TB lesions dictate the treatment-shortening potential of individual series as early as possible. The quality of leads will be assessed by measuring medicinal chemistry tractability, target novelty, ability to kill Mtb residing in caseum from granulomas and ability to be transported across lung alveolar cells. The project will advance hit series that the HIT-TB program predicted possessed characteristics needed to shorten the duration of chemotherapy, based on clinical evidence (oxazolidinones) or mechanistic novelty, where the engaged targets are predicted to play critical roles in the development of human TB pathogenesis. The program also continued screening libraries as collections with novel chemical diversity became available.