Dancing with KAT6A: Current advances and therapeutic potential in oncology of KAT6A inhibitors.

KAT6 A (lysine acetyltransferase 6 A) is a member of the MYST family of histone acetyltransferases (HATs) that plays a pivotal role in regulating gene expression through the acetylation of histones and non-histone proteins. Dysregulation of KAT6A has been implicated in various cancers, making it an attractive target for therapeutic intervention. Over the past, significant advancements have been made in the development of small-molecule KAT6A inhibitors. PF-07248144 has shown antitumor activity in estrogen receptor-positive (ER+) breast cancer models and is currently undergoing clinical evaluation. The development of these inhibitors has been facilitated by structure-based drug design and high-throughput screening, enhancing their selectivity and pharmacokinetic properties. This review provides a comprehensive overview of the structural and biological functions of KAT6A, its role in tumor progression, and the therapeutic potential of its inhibition. It summarizes the advancements in KAT6A inhibitor development from 2019 to the present, emphasizing the optimization processes from lead compounds to clinical candidates.