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

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.