A KATing Edge Perspective on KAT6A Inhibitors as Anticancer Agents
Rochelle Woodland, Adi Suwandi, Awgichew Behaile Teklemariam, Nidhish Francis, Li Li, Kenneth A. Chinkwo, Jonathan B. Baell, David J. LeaverThe development of lysine acetyltransferase (KAT) inhibitors as anticancer agents has progressed rapidly from initial tool compounds to numerous molecules entering clinical trials. The most clinically advanced KAT6A inhibitor, prifetrastat (PF‐07248144), entered Phase III clinical trials in 2025. The discovery of prifetrastat is an excellent example of instrumental contributions made by Australian biomedical and medicinal chemistry researchers to the creation of innovative and cutting‐edge anticancer therapeutics. Within this perspective we summarize KAT6A structural biology and structure–activity relationships (SAR) for acylsulfonylhydrazides, [1,2,4]thiadiazines and benzisoxazole sulfonamide inhibitors in addition to providing updates on KAT6A inhibitors that have already entered into clinical trials. Key clinical challenges and opportunities facing the field are discussed herein.