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Mycobacterium tuberculosis DprE1 Inhibitor OPC-167832 Is Active against Mycobacterium abscessus In Vitro .

Jickky Palmae SarathyMatthew D ZimmermanMartin GengenbacherVeronique Anne DartoisThomas Dick
Published in: Antimicrobial agents and chemotherapy (2022)
The antituberculosis candidate OPC-167832, an inhibitor of DprE1, was active against Mycobacterium abscessus. Resistance mapped to M. abscessus dprE1 , suggesting target retention. OPC-167832 was bactericidal and did not antagonize activity of clinical anti-M. abscessus antibiotics. Due to its moderate potency compared to that against Mycobacterium tuberculosis, the compound lacked efficacy in a mouse model and is thus not a repurposing candidate. These results identify OPC-167832-DprE1 as a lead-target couple for a M. abscessus-specific optimization program.
Keyphrases
  • mycobacterium tuberculosis
  • mouse model
  • pulmonary tuberculosis
  • quality improvement
  • high intensity