ArticleRSC medicinal chemistry2025
Design, synthesis, and structure-activity relationship studies of 4-substituted phenylpyrazolidinone derivatives as potent Ku70/80 targeted DNA-PK inhibitors.
Article in RSC medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
Funding
Abstract
The Ku70-Ku80 (Ku) heterodimer complex plays a central role in the non-homologous end joining (NHEJ) double-strand break (DSB) repair pathway and the DNA damage response (DDR). Like DNA-PK, Ku is a promising drug target for cancer treatment when combined with radiotherapy or DSB-inducing agents. We have previously reported the first-in-class, early-generation, highly potent, and specific Ku-DNA binding inhibitors (Ku-DBi's) that block the Ku interaction with DNA and inhibit DNA-PK kinase activity. These early-generation Ku-DBi's also inhibit cellular DNA-PK, NHEJ-catalyzed DSB repair, sensitize non-small cell lung cancer (NSCLC) cells to DSB-inducing agents, and potentiate the cellular effects of these agents
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