关于KAT6A抑制剂作为抗癌药物的KATing Edge视角。
完整摘要 · 中文译文
赖氨酸乙酰转移酶（KAT）抑制剂作为抗癌药物的开发，已从最初的工具化合物迅速发展为众多进入临床试验的分子。临床进展最领先的KAT6A抑制剂prifetrastat（PF-07248144）已于2025年进入III期临床试验。prifetrastat的发现是澳大利亚生物医学和药物化学研究人员在创新性前沿抗癌疗法开发中做出工具性贡献的极佳范例。在本展望中，我们总结了KAT6A结构生物学以及酰基磺酰肼类、[1,2,4]噻二嗪类和苯并异噁唑磺酰胺类抑制剂的构效关系（SAR），并提供了已进入临床试验的KAT6A抑制剂的最新进展。本文还讨论了该领域面临的关键临床挑战与机遇。
完整摘要 · 英文原文
The 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.