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

结核分枝杆菌 DprE1 抑制剂 OPC-167832 在体外对脓肿分枝杆菌有活性

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作者:Jickky Palmae Sarathy, Matthew D Zimmerman, Martin Gengenbacher, Véronique Dartois, Thomas Dick

Abstract

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.

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