The Bare Essentials of Antibiotic Target Validation

ACS Infect Dis. 2017 Jan 13;3(1):2-4. doi: 10.1021/acsinfecdis.6b00185. Epub 2016 Nov 9.


The convergence of competitive fitness experiments and phenotypic screening would seem to be an auspicious beginning for validation of an antibacterial target. IMPDH was already identified an essential protein in Mycobacterium tuberculosis when not one, but two, groups discovered inhibitors with promising antitubercular activity. A new target appeared to be born. Surprisingly, the two groups came to completely different conclusions about the vulnerability of IMPDH and its future as a drug target. This viewpoint discusses these papers and how to resolve this conundrum.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Drug Design
  • Drug Discovery*
  • Drug Evaluation, Preclinical
  • Humans
  • IMP Dehydrogenase / antagonists & inhibitors*
  • Models, Molecular
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / enzymology*
  • Protein Conformation
  • Reproducibility of Results


  • Antitubercular Agents
  • IMP Dehydrogenase