Center for Tuberculosis Research, Division of Infectious Diseases, Johns Hopkins Universitygrid.21107.35grid.471401.7grid.21107.35 School of Medicine, Baltimore, Maryland, USA.
Diseases of the Developing World, GlaxoSmithKline R+D Limited, Tres Cantos, Madrid, Spain.
Antimicrob Agents Chemother. 2022 Jun 21;66(6):e0013222. doi: 10.1128/aac.00132-22. Epub 2022 May 24.
As a result of a high-throughput compound screening campaign using Mycobacterium tuberculosis-infected macrophages, a new drug candidate for the treatment of tuberculosis has been identified. GSK2556286 inhibits growth within human macrophages (50% inhibitory concentration [IC] = 0.07 μM), is active against extracellular bacteria in cholesterol-containing culture medium, and exhibits no cross-resistance with known antitubercular drugs. In addition, it has shown efficacy in different mouse models of tuberculosis (TB) and has an adequate safety profile in two preclinical species. These features indicate a compound with a novel mode of action, although still not fully defined, that is effective against both multidrug-resistant (MDR) or extensively drug-resistant (XDR) and drug-sensitive (DS) M. tuberculosis with the potential to shorten the duration of treatment in novel combination drug regimens. (This study has been registered at ClinicalTrials.gov under identifier NCT04472897).
在一项使用结核分枝杆菌感染的巨噬细胞进行的高通量化合物筛选活动中,发现了一种新的结核病治疗候选药物。GSK2556286 抑制人巨噬细胞内的生长(半数抑制浓度 [IC] = 0.07 μM),对含胆固醇培养基中的细胞外细菌具有活性,并且与已知的抗结核药物没有交叉耐药性。此外,它在不同的结核分枝杆菌(TB)小鼠模型中表现出疗效,并且在两种临床前物种中具有足够的安全性特征。这些特征表明该化合物具有一种尚未完全定义的新型作用模式,对多药耐药(MDR)或广泛耐药(XDR)和药物敏感(DS)结核分枝杆菌均有效,有可能缩短新型联合药物方案的治疗时间。(该研究已在 ClinicalTrials.gov 上注册,标识符为 NCT04472897)。