The enzymes isocitrate lyase (ICL) isoforms 1 and 2 are essential for Mycobacterium tuberculosis survival within macrophages during latent tuberculosis (TB). As such, ICLs are attractive therapeutic targets for the treatment of tuberculosis. However, there are few biophysical assays that are available for accurate kinetic and inhibition studies of ICL in vitro. Herein we report the development of a combined NMR spectroscopy and thermal shift assay to study ICL inhibitors for both screening and inhibition constant (IC₅₀) measurement. Operating this new assay in tandem with virtual high-throughput screening has led to the discovery of several new ICL1 inhibitors.

中文翻译：

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用于评估结核分枝杆菌异柠檬酸裂解酶抑制剂的NMR和热位移分析方法的发展

异柠檬酸裂合酶（ICL）同工型1和2对潜伏性结核病（TB）期间巨噬细胞内结核分枝杆菌的生存至关重要。这样，ICL是治疗结核病的有吸引力的治疗靶标。然而，很少有生物物理测定可用于体外ICL的准确动力学和抑制研究。在本文中，我们报告了结合NMR光谱和热位移测定法的发展，以研究用于筛选和抑制常数（IC ₅₀）测量的ICL抑制剂。与虚拟高通量筛选协同操作运行此新测定法，导致发现了几种新的ICL1抑制剂。