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November 15, 2024
2024 WARF Therapeutics Distinguished Lecture in Drug Discovery
- Jeffrey Aube, PhD
- University of North Carolina
New Approaches to Tuberculosis Therapeutics
Tuberculosis (TB) continues to be a major worldwide health problem, despite the existence of numerous drugs for its treatment. This is in part due to the long therapeutics times required to administer cocktails of front-line therapeutics and in part due to the emergence of even more challenging long-term strains. For these reasons, new therapeutic agents for the treatment of TB continue to be sought. In collaborative work with the laboratory of Carl Nathan (Weill–Cornell Medicine) and others, we have sought to find new chemotypes as potential anti-TB agents and to identify new biochemical targets for drug treatment. In this talk, I will describe our efforts in this area, beginning with early approaches to explore beta-lactam antibiotics as possible TB agents. More recent efforts have been focused on finding inhibitors of phosphopantetheinyl transferase (PptT). PptT carries out central biochemistry that is essential for mycobacterial survival; for this reason, it has been a long sought-target for antibacterial agent development. This story begins with our team's discovery of the first effective small-molecule inhibitors of PptT, efforts to use bioisostere design to create a new series, and more recent chemotypes of PptT.
Hosted by Jennifer Golden
