结核分枝杆菌 DprE1 抑制剂 OPC-167832 对脓肿分枝杆菌有效。
Mycobacterium tuberculosis DprE1 Inhibitor OPC-167832 Is Active against Mycobacterium abscessus .
机构信息
Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA.
Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, New Jersey, USA.
出版信息
Antimicrob Agents Chemother. 2022 Dec 20;66(12):e0123722. doi: 10.1128/aac.01237-22. Epub 2022 Nov 9.
The antituberculosis candidate OPC-167832, an inhibitor of DprE1, was active against Mycobacterium abscessus. Resistance mapped to M. abscessus , 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.
抗结核候选药物 OPC-167832 是一种 DprE1 抑制剂,对脓肿分枝杆菌具有活性。耐药性与脓肿分枝杆菌有关,提示靶标保留。OPC-167832 具有杀菌作用,不拮抗临床抗脓肿分枝杆菌抗生素的活性。由于其对结核分枝杆菌的效力与结核分枝杆菌相比中等,该化合物在小鼠模型中无效,因此不是一种再利用候选药物。这些结果将 OPC-167832-DprE1 确定为一种针对脓肿分枝杆菌的特异性优化方案的先导靶标对。