Target-guided screening of fragments (TGSOF) was developed and employed in the identification of EV-A71 3C protease (3C^pro) inhibitors. We identified 4-acetylpyridine and 3-acetylpyridine as effective P3 fragments of an inhibitor and obtained the corresponding irreversible inhibitors 12c and 12fvia this method. Furthermore, based on 12c and 12f, we have obtained reversible inhibitors 17c and 17f. These results demonstrated that TGSOF is a useful strategy for identifying suitable fragments in developing leads in drug discovery.

中文翻译：

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在发现针对EV-A71 3C蛋白酶的抑制剂中进行片段指导的片段筛选（TGSOF）

开发了靶向指导的片段筛选（TGSOF），并用于鉴定EV-A71 3C蛋白酶（3C ^pro）抑制剂。我们鉴定出4-乙酰基吡啶和3-乙酰基吡啶为抑制剂的有效P3片段，并通过该方法获得了相应的不可逆抑制剂12c和12f。此外，基于12c和12f，我们获得了可逆抑制剂17c和17f。这些结果表明，TGSOF是在药物开发中的先导中鉴定合适片段的有用策略。