Structural and mechanistic study of a novel inhibitor analogue of <i>M. tuberculosis</i> cytochrome bc₁:aa₃.

ABSTRACT: Drug-resistant tuberculosis (TB) continues to challenge treatment options, necessitating the exploration of new compounds of novel targets. The mycobacterial respiratory complex cytochrome bc₁:aa₃ has emerged as a promising target, exemplified by the success of first-in-class inhibitor Q203 in phase 2 clinical trials. However, to fully exploit the potential of this target and to identify the best-in-class inhibitor more compounds need evaluation. Here, we introduce JNJ-2901, a novel Q203 analogue, that demonstrates activity against multidrug-resistant M. tuberculosis clinical strains at sub-nanomolar concentration and 4-log reduction in bacterial burden in a mouse model of TB infection. Inhibitory studies on purified enzymes validate the nanomolar inhibitions o

SUBMITTER: Verma AK 

PROVIDER: S-EPMC11964921 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature