がん治療のためのATR阻害剤の最近の開発

Ataxia Telangiectasia and Rad3-related (ATR) kinase belongs to the PIKK (phosphatidylinositol 3-kinase-related kinase) family and serves as a pivotal hub for preserving genomic stability and regulating responses to replication stress and DNA damage. Dysregulation of ATR signaling is strongly associated with tumorigenesis, resistance to therapy, and other pathological states (such as neurodegenerative diseases), making it a highly attractive target in cancer therapy. To date, no ATR inhibitors have achieved regulatory approval; however, several candidate molecules, most notably berzosertib, ceralasertib, and gartisertib, are advancing in clinical trials. This review focuses on the medicinal chemistry progress in ATR inhibitor development since 2018. Throughout this review, we systematically interweave major chemical scaffolds. We anticipate that this review will offer insightful guidance for rational design of future ATR inhibitors and help accelerate the emergence of next-generation ATR inhibitors with superior potency, selectivity, and clinical feasibility.