Development and therapeutic potential of DNA-dependent protein kinase inhibitors.
Fiche publication
Date publication
juin 2024
Journal
Bioorganic chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GARRIDO Carmen, Pr LIRUSSI Frédéric
Tous les auteurs :
Hui Z, Deng H, Zhang X, Garrido C, Lirussi F, Ye XY, Xie T, Liu ZQ
Lien Pubmed
Résumé
The deployment of DNA damage response (DDR) combats various forms of DNA damage, ensuring genomic stability. Cancer cells' propensity for genomic instability offers therapeutic opportunities to selectively kill cancer cells by suppressing the DDR pathway. DNA-dependent protein kinase (DNA-PK), a nuclear serine/threonine kinase, is crucial for the non-homologous end joining (NHEJ) pathway in the repair of DNA double-strand breaks (DSBs). Therefore, targeting DNA-PK is a promising cancer treatment strategy. This review elaborates on the structures of DNA-PK and its related large protein, as well as the development process of DNA-PK inhibitors, and recent advancements in their clinical application. We emphasize our analysis of the development process and structure-activity relationships (SARs) of DNA-PK inhibitors based on different scaffolds. We hope this review will provide practical information for researchers seeking to develop novel DNA-PK inhibitors in the future.
Mots clés
Cancer therapy, DDR, DNA-PK, SAR, Small molecule inhibitors
Référence
Bioorg Chem. 2024 06 29;150:107608