Lysine acetyltransferases (KATs) are a family of epigenetic enzymes involved in the regulation of gene expression; they represent a promising class of emerging drug targets. The frequent molecular dysregulation of these enzymes, as well as their mechanistic links to biological functions that are crucial to cancer, have led to exploration around the development of small-molecule inhibitors against KATs. Despite early challenges, recent advances have led to the development of potent and selective enzymatic and bromodomain (BRD) KAT inhibitors. In this review we discuss the discovery and development of new KAT inhibitors and their application as oncology therapeutics. Additionally, new chemically induced proximity approaches are presented, offering opportunities for unique target selectivity profiles and tissue-specific targeting of KATs. Emerging clinical data for CREB binding protein (CREBBP)/EP300 BRD inhibitors and KAT6 catalytic inhibitors indicate the promise of this target class in cancer therapeutics.

中文翻译：

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组蛋白赖氨酸乙酰转移酶抑制剂：一类新兴的癌症治疗药物

赖氨酸乙酰转移酶 (KAT) 是参与基因表达调节的表观遗传酶家族；它们代表了一类有前途的新兴药物靶点。这些酶频繁的分子失调，以及它们与癌症至关重要的生物功能的机制联系，引发了围绕 KAT 小分子抑制剂开发的探索。尽管存在早期挑战，但最近的进展导致了有效且选择性的酶和溴结构域 (BRD) KAT 抑制剂的开发。在这篇综述中，我们讨论了新型 KAT 抑制剂的发现和开发及其在肿瘤治疗中的应用。此外，还提出了新的化学诱导邻近方法，为 KAT 的独特靶点选择性和组织特异性靶向提供了机会。CREB ​​结合蛋白 (CREBBP)/EP300 BRD 抑制剂和 KAT6 催化抑制剂的新临床数据表明了此类靶标在癌症治疗中的前景。