Abstract：
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.
摘要：
赖氨酸乙酰转移酶（KATs）是一类参与基因表达调控的表观遗传酶；它们代表了一类有希望的新兴药物靶标。这些酶频繁的分子失调,以及它们与对癌症至关重要的生物学功能的机械联系，已经导致围绕开发针对KATs的小分子抑制剂的探索。尽管早期的挑战，最近的进展导致了有效和选择性的酶和溴结构域(BRD)KAT抑制剂的开发。在这篇综述中，我们讨论了新的KAT抑制剂的发现和开发及其在肿瘤治疗中的应用。此外,提出了新的化学诱导邻近方法，提供独特的靶标选择性概况和组织特异性靶向KATs的机会。CREB结合蛋白（CREBBP）/EP300BRD抑制剂和KAT6催化抑制剂的新兴临床数据表明该靶标类别在癌症治疗中的前景。
