Folate Biosynthesis Inhibitors

AstraZeneca has developed and optimized a high throughput assay that monitors the conversion of substrate to product of the selected enzyme. A screen has been performed, and active compounds have been identified. Next steps: The validated hits identified in the screen referenced above will be prioritized for hit-to-lead work based on criteria including activity and chemical tractability, supplemented by additional information including in vitro ADMET responses. Further progression of compound/series to lead optimization will be based on the demonstration of efficacy in vivo in an acute TB model.