A new 'golden age" for the antitubercular target InhA Articles uri icon

authors

  • ROZMAN, KAJA
  • SOSIC, IZIDOR
  • FERNANDEZ, RAQUEL
  • YOUNG, ROBERT J.
  • MENDOZA LOSANA, ALFONSO
  • GOBEC, STANILSLAV
  • ENCINAS, LOURDES

publication date

  • March 2017

start page

  • 492

end page

  • 502

issue

  • 3

volume

  • 22

International Standard Serial Number (ISSN)

  • 1359-6446

Electronic International Standard Serial Number (EISSN)

  • 1878-5832

abstract

  • The increasing prevalence of multidrug-resistant strains of Mycobacterium
    tuberculosis is the main contributing factor in unfavorable outcomes in the
    treatment of tuberculosis. Studies suggest that direct inhibitors of InhA, an
    enoyl-ACP-reductase, might yield promising clinical candidates that can
    be developed into new antitubercular drugs. In this review, we describe the
    application of different hit-identification strategies to InhA, which clearly
    illustrate the druggability of its active site through distinct binding
    mechanisms. We further characterize four classes of InhA inhibitors that
    show novel binding modes, and provide evidence of their successful target
    engagement as well as their in vivo activity