一种新型结核分枝杆菌 InhA 变构抑制剂在 C3HeB/FeJ 小鼠模型中的疗效及耐药潜能研究
Efficacy and Improved Resistance Potential of a Cofactor-Independent InhA Inhibitor of Mycobacterium tuberculosis in the C3HeB/FeJ Mouse Model.
机构信息
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA.
出版信息
Antimicrob Agents Chemother. 2019 Mar 27;63(4). doi: 10.1128/AAC.02071-18. Print 2019 Apr.
AN12855 is a direct, cofactor-independent inhibitor of InhA in In the C3HeB/FeJ mouse model with caseous necrotic lung lesions, AN12855 proved efficacious with a significantly lower resistance frequency than isoniazid. AN12855 drug levels were better retained in necrotic lesions and caseum where the majority of hard to treat, extracellular bacilli reside. Owing to these combined attributes, AN12855 represents a promising alternative to the frontline antituberculosis agent isoniazid.
AN12855 是 InhA 的直接、辅因子非依赖性抑制剂。在 C3HeB/FeJ 鼠伴有干酪样坏死性肺病变的模型中，AN12855 显示出疗效，其耐药频率明显低于异烟肼。AN12855 药物水平在坏死病变和干酪样物中保留更好，而大部分难以治疗的细胞外细菌存在于其中。由于这些综合特性，AN12855 代表了一种有前途的替代一线抗结核药物异烟肼的选择。
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