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Daphnegiravone D (DGD) is a natural compound derived from *Daphne giraldii* that has demonstrated antineoplastic activity against hepatocellular carcinoma (HCC). The compound works by targeting Ataxia telangiectasia and Rad3-related protein (ATR), a critical enzyme involved in DNA damage response pathways. DGD induces apoptosis and oxidative stress in HCC cells through ATR inhibition, leading to increased reactive oxygen species (ROS) production and cell death. Molecular docking studies and cellular thermal shift assays have confirmed that DGD directly binds to ATR protein. The compound shows enhanced antitumor effects when combined with chemotherapy agents such as oxaliplatin, with the combination increasing both apoptosis and ROS production beyond either drug alone[2]. The mechanism involves disruption of DNA damage response, cell cycle regulation, and DNA repair pathways that are dependent on ATR function[2].
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