Responsible for interpreting histone post-translational modifications, epigenetic reader proteins have emerged as novel therapeutic targets for a wide range of diseases. Chemical probes have been critical in enabling target validation studies and have led to translational advances in cancer and inflammation-related pathologies. Here, we present the most recently reported probes of reader proteins that recognize acylated and methylated lysine. We will discuss challenges associated with achieving potent antagonism of reader domains and review ongoing efforts to overcome these hurdles, focusing on targeting strategies including the use of peptidomimetic ligands, allosteric modulators, and protein degraders.

中文翻译：

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用于靶向乙酰化和甲基化赖氨酸的表观遗传阅读器结构域的改进方法。

负责解释组蛋白翻译后修饰的表观遗传阅读蛋白已成为多种疾病的新治疗靶点。化学探针对于实现目标验证研究至关重要，并导致癌症和炎症相关病理学的转化进展。在这里，我们介绍了最近报道的识别酰化和甲基化赖氨酸的阅读器蛋白探针。我们将讨论与实现有效对抗读者域相关的挑战，并回顾为克服这些障碍而正在进行的努力，重点关注靶向策略，包括使用拟肽配体、变构调节剂和蛋白质降解剂。