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Antibacterial agents

New routes to tuberculosis treatment

Nature Reviews Drug Discovery volume 16, pages 600–601 (2017)Cite this article

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Mycolic acids are long-chain α-branched-β-hydroxylated fatty acids that are found in the cell wall of M. tuberculosis and are critical for viability and virulence. In M. tuberculosis, mycolic acid biosynthesis involves over 20 enzymes, including polyketide synthase 13 (Pks13), which carries out the final step. Sacchettini and colleagues therefore set out to investigate the therapeutic potential of Pks13 inhibition.

Using structure-guided approaches, the authors improved the potency and pharmacological properties of the previously identified benzofuran derivative TAM1, which is active against M. tuberculosis and inhibits the C-terminal thioesterase domain activity of Pks13, leading to the development of a highly potent and safe lead compound, TAM16.

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References

  1. Aggarwal, A. et al. Development of a novel lead that targets M. tuberculosis polyketide synthase 13. Cell 170, 249–259.E25 (2017)

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  2. Wellington, S. et al. A small-molecule allosteric inhibitor of Mycobacterium tuberculosis tryptophan synthase. Nat. Chem. Biol. http://dx.doi.org/10.1038/nchembio.2420 (2017)

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Authors
  1. Sarah Crunkhorn
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Crunkhorn, S. New routes to tuberculosis treatment. Nat Rev Drug Discov 16, 600–601 (2017). https://doi.org/10.1038/nrd.2017.156

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  • DOI: https://doi.org/10.1038/nrd.2017.156

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