We review progress in the application of fragment-based drug discovery (FBDD) to epigenetic drug discovery (EPIDD) targeted at epigenetic writer and eraser enzymes as well as reader domains over the last 15 years. The greatest successes to date are in prospecting for bromodomain binding ligands. From a diverse array of fragment hits, multiple potent and selective compounds ensued, including the oncology clinical candidates mivebresib, ABBV-744, pelabresib, and PLX51107.

中文翻译：

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从命中寻找到魔法子弹：表观遗传和基于片段的药物发现的成功结合 (EPIDD + FBDD)

我们回顾了过去 15 年来基于片段的药物发现 (FBDD) 应用于表观遗传药物发现 (EPIDD) 的进展，针对表观遗传写入酶和擦除酶以及读取域。迄今为止最大的成功是在寻找溴结构域结合配体。从各种片段命中中，产生了多种有效和选择性的化合物，包括肿瘤临床候选药物 mivebresib、ABBV-744、pelabresib 和 PLX51107。