ReviewPost screenLearning from the past for TB drug discovery in the future

- We explain the shift from target-based to phenotypic HTS for TB.
- We describe EU-funded FP7 collaborations, NM4TB and MM4TB projects.
- We detail the success with DprE1 and failure with PimA.
- We suggest how we can learn from earlier in vitro and in vivo efforts and data.
- We propose future approaches to TB drug discovery.

Tuberculosis drug discovery has shifted in recent years from a primarily target-based approach to one that uses phenotypic high-throughput screens. As examples of this, through our EU-funded FP7 collaborations, New Medicines for Tuberculosis was target-based and our more-recent More Medicines for Tuberculosis project predominantly used phenotypic screening. From these projects we have examples of success (DprE1) and failure (PimA) going from drug to target and from target to drug, respectively. It is clear that we still have much to learn about the drug targets and the complex effects of the drugs on Mycobacterium tuberculosis. We propose a more integrated approach that learns from earlier drug discovery efforts that could help to move drug discovery forward.