Abstract
Tuberculosis (TB) remains the world's leading cause of death due to an infectious agent. Increased disease burden coupled with the rise in multi-drug-resistant TB (MDR-TB) urgently calls for new drugs with novel mechanisms of action to combat this global health crisis. The Hedstrom lab has been searching for an inhibitor for MtbIMPDH2, an attractive but currently unexploited drug target. During this search, an uncharacterized essential enzyme, MtbPanG was discovered. PanG catalyzes a key step in Mtb’s essential pantothenate/CoA biosynthetic pathway, making it an attractive potential drug target. Here, we describe the characterization of PanG as an antitubercular target and present four PanG inhibitors. Additionally, we report the continued search for an IMPDH2 inhibitor with the screening of a novel class of morpholine-based IMPDH2 inhibitors.